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Outputs (264)

Digital pathology for reporting histopathology samples, including cancer screening samples – definitive evidence from a multisite study (2024)
Journal Article
Azam, A. S., Tsang, Y., Thirlwall, J., Kimani, P. K., Sah, S., Gopalakrishnan, K., …Snead, D. R. J. (2024). Digital pathology for reporting histopathology samples, including cancer screening samples – definitive evidence from a multisite study. Histopathology, 84(5), 847-862. https://doi.org/10.1111/his.15129

Aims: To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples. Methods: A total of 2024 cases (608 breast, 607 GI, 6... Read More about Digital pathology for reporting histopathology samples, including cancer screening samples – definitive evidence from a multisite study.

Quantitative expression of oestrogen receptor in breast cancer: Clinical and molecular significance (2023)
Journal Article
Makhlouf, S., Quinn, C., Toss, M., Alsaleem, M., Atallah, N. M., Ibrahim, A., …Rakha, E. A. (2024). Quantitative expression of oestrogen receptor in breast cancer: Clinical and molecular significance. European Journal of Cancer, 197, Article 113473. https://doi.org/10.1016/j.ejca.2023.113473

Background Oestrogen receptor (ER) positive breast cancer (BC) patients are eligible for endocrine therapy (ET), regardless of ER immunohistochemical expression level. There is a wide spectrum of ER expression and the response to ET is not uniform... Read More about Quantitative expression of oestrogen receptor in breast cancer: Clinical and molecular significance.

The amino acid transporter SLC7A11 expression in breast cancer (2023)
Journal Article
Nath, P., Alfarsi, L. H., El-Ansari, R., Masisi, B. K., Erkan, B., Fakroun, A., …Green, A. R. (2024). The amino acid transporter SLC7A11 expression in breast cancer. Cancer Biology and Therapy, 25(1), Article 2291855. https://doi.org/10.1080/15384047.2023.2291855

Breast cancer (BC), characterized by its diverse molecular profiles and clinical outcomes, presents a significant challenge in the development of effective therapeutic strategies. Metabolic reprogramming, a defining characteristic of cancer, has emer... Read More about The amino acid transporter SLC7A11 expression in breast cancer.

Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways (2023)
Journal Article
Saidy, B., Vasan, R., Durant, R., Greener, M., Immanuel, A., Green, A. R., …Storr, S. J. (2023). Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways. Scientific Reports, 13(1), Article 21163. https://doi.org/10.1038/s41598-023-48198-y

DARPP-32 is a key regulator of protein-phosphatase-1 (PP-1) and protein kinase A (PKA), with its function dependent upon its phosphorylation state. We previously identified DKK1 and GRB7 as genes with linked expression using Artificial Neural Network... Read More about Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways.

Characterisation of luminal and triple-negative breast cancer with HER2 Low protein expression (2023)
Journal Article
Atallah, N. M., Haque, M., Quinn, C., Toss, M. S., Makhlouf, S., Ibrahim, A., …Rakha, E. (2023). Characterisation of luminal and triple-negative breast cancer with HER2 Low protein expression. European Journal of Cancer, 195, Article 113371. https://doi.org/10.1016/j.ejca.2023.113371

Background: Breast cancer (BC) expressing low levels of human epidermal growth factor receptor 2 (HER2 Low) is an emerging category that needs further refining. This study aims to provide a comprehensive clinico-pathological and molecular profile of... Read More about Characterisation of luminal and triple-negative breast cancer with HER2 Low protein expression.

Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level (2023)
Journal Article
Atallah, N. M., Alsaleem, M., Toss, M. S., Mongan, N. P., & Rakha, E. (2023). Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level. British Journal of Cancer, https://doi.org/10.1038/s41416-023-02426-4

Background: Increasing data indicate that HER2-positive (HER2 +) breast cancer (BC) subtypes exhibit differential responses to targeted anti-HER2 therapy. This study aims to investigate these differences and the potential underlying molecular mechani... Read More about Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level.

Obesity-associated changes in molecular biology of primary breast cancer (2023)
Journal Article
Nguyen, H., Geukens, T., Maetens, M., Aparicio, S., Bassez, A., Borg, A., …Desmedt, C. (2023). Obesity-associated changes in molecular biology of primary breast cancer. Nature Communications, 14, Article 4418. https://doi.org/10.1038/s41467-023-39996-z

Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs acc... Read More about Obesity-associated changes in molecular biology of primary breast cancer.

The clinical and biological significance of estrogen receptor-low positive breast cancer (2023)
Journal Article
Makhlouf, S., Althobi, M., Toss, M., Muftah, A. A., Mongan, N. P., Lee, A. H. S., …Rakha, E. A. (2023). The clinical and biological significance of estrogen receptor-low positive breast cancer. Modern Pathology, 36(10), Article 100284. https://doi.org/10.1016/j.modpat.2023.100284

Estrogen Receptor (ER) status in breast cancer (BC) is determined using immunohistochemistry (IHC) with nuclear expression in ≥1% of cells defined as ER-positive. BC with 1-9% expression (ER-low positive), is a clinically and biologically unique subg... Read More about The clinical and biological significance of estrogen receptor-low positive breast cancer.

Encapsulated papillary carcinoma of the breast: does it have a native basement membrane? (2023)
Journal Article
Ghannam, S. F., Rutland, C. S., Allegrucci, C., Mongan, N. P., & Rakha, E. (2023). Encapsulated papillary carcinoma of the breast: does it have a native basement membrane?. Histopathology, 83(3), 376-393. https://doi.org/10.1111/his.14939

Background Encapsulated papillary carcinoma (EPC) is surrounded by a thick fibrous capsule-like structure, which is interpreted as a thickened basement membrane (BM). This study aimed to describe the geometric characteristics of the EPC capsule and... Read More about Encapsulated papillary carcinoma of the breast: does it have a native basement membrane?.

Characteristics and prognostic significance of polo-like kinase-1 (PLK1) expression in breast cancer (2023)
Journal Article
Lashen, A. G., Toss, M. S., Wootton, L., Green, A. R., Mongan, N. P., Madhusudan, S., & Rakha, E. (2023). Characteristics and prognostic significance of polo-like kinase-1 (PLK1) expression in breast cancer. Histopathology, 83(3), 414-425. https://doi.org/10.1111/his.14960

Background: Polo-like kinase-1 (PLK1) plays a crucial role in cell cycle progression,and it is considered a potential therapeutic target in many cancers. Although the role of PLK1 is well established in triple negative breast cancer (TNBC) as an onco... Read More about Characteristics and prognostic significance of polo-like kinase-1 (PLK1) expression in breast cancer.

Targeting DNA damage repair precision medicine strategies in cancer (2023)
Journal Article
Brownlie, J., Kulkarni, S., Algethami, M., Jeyapalan, J. N., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2023). Targeting DNA damage repair precision medicine strategies in cancer. Current Opinion in Pharmacology, 70, Article 102381. https://doi.org/10.1016/j.coph.2023.102381

DNA repair targeted therapeutics is a promising precision medicine strategy in cancer. The development and clinical use of PARP inhibitors has transformed lives for many patients with BRCA germline deficient breast and ovarian cancer as well as plati... Read More about Targeting DNA damage repair precision medicine strategies in cancer.

High Inner Centromere Protein Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer (2023)
Journal Article
Ibrahim, A., Miligy, I. M., Toss, M. S., Green, A. R., & Rakha, E. A. (2023). High Inner Centromere Protein Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer. Pathobiology, 90(6), 377–388. https://doi.org/10.1159/000529628

Introduction: Inner centromere protein (INCENP) is a member of the chromosomal passenger complex (CPC) and plays a key role in mitosis and cell proliferation. This study aims to evaluate the clinical and prognostic significance of INCENP in invasive... Read More about High Inner Centromere Protein Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer.

A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease (2023)
Journal Article
Storr, S. J., Hoskin, V., Aiyappa‐Maudsley, R., Ghaffari, A., Varma, S., Green, A., …Martin, S. G. (2023). A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease. Cancer Medicine, 12(9), 10908-10916. https://doi.org/10.1002/cam4.5802

Introduction: The cytoskeletal protein ezrin is upregulated in many cancer types and is strongly associated with poor patient outcome. While the clinical and prognostic value of ezrin has been previously evaluated in breast cancer, most studies to da... Read More about A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease.

RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer (2023)
Journal Article
Ciscar, M., Trinidad, E. M., Perez-Chacon, G., Alsaleem, M., Jimenez, M., Jimenez-Santos, M. J., …Gonzalez-Suarez, E. (2023). RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer. EMBO Molecular Medicine, 15(4), Article e16715. https://doi.org/10.15252/emmm.202216715

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein ex... Read More about RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer.

Combined proliferation and apoptosis index provides better risk stratification in breast cancer (2023)
Journal Article
Ibrahim, A., Toss, M. S., Atallah, N. M., Al Saleem, M., Green, A. R., & Rakha, E. A. (2023). Combined proliferation and apoptosis index provides better risk stratification in breast cancer. Histopathology, 82(7), 1029-1047. https://doi.org/10.1111/his.14887

Aims: Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision-making. Despite the well-established prognostic value of cellular proliferation in BC, the interplay between proliferation and apoptosis... Read More about Combined proliferation and apoptosis index provides better risk stratification in breast cancer.

Expression, assessment and significance of Ki67 expression in breast cancer: an update (2023)
Journal Article
Lashen, A. G., Toss, M. S., Ghannam, S. F., Makhlouf, S., Green, A., Mongan, N. P., & Rakha, E. (2023). Expression, assessment and significance of Ki67 expression in breast cancer: an update. Journal of Clinical Pathology, 76(6), Article 357-364. https://doi.org/10.1136/jcp-2022-208731

Ki67 expression is one of the most important and cost-effective surrogate markers to assess for tumour cell proliferation in breast cancer (BC). The Ki67 labelling index has prognostic and predictive value in patients with early-stage BC, particularl... Read More about Expression, assessment and significance of Ki67 expression in breast cancer: an update.

The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up (2023)
Journal Article
Lashen, A. G., Toss, M. S., Mongan, N. P., Green, A. R., & Rakha, E. A. (2023). The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up. Cancer, 129(8), 1183-1194. https://doi.org/10.1002/cncr.34655

Background: The routine assessment of progesterone receptor (PR) expression in breast cancer (BC) remains controversial. This study aimed to evaluate the role of PR expression in luminal BC, with emphasis on the definition of positivity and its progn... Read More about The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up.

Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer (2023)
Journal Article
Lothion-Roy, J., Haigh, D. B., Harris, A. E., Metzler, V. M., Alsaleem, M., Toss, M. S., …Woodcock, C. L. (2023). Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer. Frontiers in Genetics, 13, Article 1096071. https://doi.org/10.3389/fgene.2022.1096071

N6-methyladenosine (m6A) is the most abundant internal mRNA modification and is dynamically regulated through distinct protein complexes that methylate, demethylate, and/or interpret the m6A modification. These proteins, and the m6A modification, are... Read More about Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer.

The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer (2023)
Journal Article
Metzler, V. M., de Brot, S., Haigh, D. B., Woodcock, C. L., Lothion-Roy, J., Harris, A. E., …Jeyapalan, J. N. (2023). The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer. Frontiers in Cell and Developmental Biology, 11, Article 1116424. https://doi.org/10.3389/fcell.2023.1116424

Histone H3 lysine 4 (H3K4) methylation is key epigenetic mark associated with active transcription and is a substrate for the KDM1A/LSD1 and KDM5B/JARID1B lysine demethylases. Increased expression of KDM1A and KDM5B is implicated in many cancer types... Read More about The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer.

Evolving DNA repair synthetic lethality targets in cancer (2022)
Journal Article
Kulkarni, S., Brownlie, J., Jeyapalan, J. N., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2022). Evolving DNA repair synthetic lethality targets in cancer. Bioscience Reports, 42(12), Article BSR20221713. https://doi.org/10.1042/BSR20221713

DNA damage signaling response and repair (DDR) is a critical defense mechanism against genomic instability. Impaired DNA repair capacity is an important risk factor for cancer development. On the other hand, up-regulation of DDR mechanisms is a featu... Read More about Evolving DNA repair synthetic lethality targets in cancer.

The clinical significance of cyclin B1 (CCNB1) in invasive breast cancer with emphasis on its contribution to lymphovascular invasion development (2022)
Journal Article
Aljohani, A. I., Toss, M. S., Green, A. R., & Rakha, E. (2023). The clinical significance of cyclin B1 (CCNB1) in invasive breast cancer with emphasis on its contribution to lymphovascular invasion development. Breast Cancer Research and Treatment, 198, 423-435. https://doi.org/10.1007/s10549-022-06801-2

Background Lymphovascular invasion (LVI) is regulated through complex molecular mechanisms. Cyclin B1 (CCNB1) was previously determined as being associated with LVI using large cohorts of breast cancer (BC) and artificial neural network (ANN) techni... Read More about The clinical significance of cyclin B1 (CCNB1) in invasive breast cancer with emphasis on its contribution to lymphovascular invasion development.

A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients (2022)
Journal Article
Xu, Q., Kaur, J., Wylie, D., Mittal, K., Li, H., Kolachina, R., …Aneja, R. (2022). A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients. International Journal of Molecular Sciences, 23(21), Article 13322. https://doi.org/10.3390/ijms232113322

Extensive intratumoral heterogeneity (ITH) is believed to contribute to therapeutic failure and tumor recurrence, as treatment-resistant cell clones can survive and expand. However, little is known about ITH in triple-negative breast cancer (TNBC) be... Read More about A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients.

Defining invasion in breast cancer: the role of basement membrane (2022)
Journal Article
Ghannam, S. F., Rutland, C. S., Allegrucci, C., Mongan, N. P., & Rakha, E. (2022). Defining invasion in breast cancer: the role of basement membrane. Journal of Clinical Pathology, https://doi.org/10.1136/jcp-2022-208584

Basement membrane (BM) is an amorphous, sheet-like structure separating the epithelium from the stroma. BM is characterised by a complex structure comprising collagenous and non-collagenous proteoglycans and glycoproteins. In the breast, the thicknes... Read More about Defining invasion in breast cancer: the role of basement membrane.

Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer (2022)
Journal Article
Harris, A. E., Metzler, V. M., Lothion-Roy, J., Varun, D., Woodcock, C. L., Haigh, D. B., …Jeyapalan, J. N. (2022). Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer. Frontiers in Endocrinology, 13, Article 1006101. https://doi.org/10.3389/fendo.2022.1006101

Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bic... Read More about Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer.

The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer (2022)
Journal Article
Haigh, D. B., Woodcock, C. L., Lothion-Roy, J., Harris, A. E., Metzler, V. M., Persson, J. L., …Mongan, N. P. (2022). The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer. Cancers, 14(20), Article 5148. https://doi.org/10.3390/cancers14205148

Prostate cancer (PCa) is a leading cause of cancer-related deaths and is driven by aberrant androgen receptor (AR) signalling. For this reason, androgen deprivation therapies (ADTs) that suppress androgen-induced PCa progression either by preventing... Read More about The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer.

Ki67 assessment in invasive luminal breast cancer: a comparative study between different scoring methods (2022)
Journal Article
Lashen, A., Toss, M. S., Green, A. R., Mongan, N. P., & Rakha, E. (2022). Ki67 assessment in invasive luminal breast cancer: a comparative study between different scoring methods. Histopathology, 81(6), 786-798. https://doi.org/10.1111/his.14781

Background: Ki67 reflects the proliferation activity in breast cancer (BC). However, an optimal method for its assessment in clinical settings has yet to be robustly defined. In this study, we compared several methods to score Ki67 to identify a reli... Read More about Ki67 assessment in invasive luminal breast cancer: a comparative study between different scoring methods.

Refining the definition of HER2-low class in invasive breast cancer (2022)
Journal Article
Atallah, N. M., Toss, M. S., Green, A. R., Mongan, N. P., Ball, G., & Rakha, E. A. (2022). Refining the definition of HER2-low class in invasive breast cancer. Histopathology, 81(6), 770-785. https://doi.org/10.1111/his.14780

Background: Emerging evidence indicates that breast cancer (BC) patients whose tumours express HER2 protein without HER2 gene amplification (HER2-low), can benefit from antibody–drug conjugates (ADC). However, the current definition of HER2-low BC re... Read More about Refining the definition of HER2-low class in invasive breast cancer.

Aurora Kinase A Is an Independent Predictor of Invasive Recurrence in Breast Ductal Carcinoma in situ (2022)
Journal Article
Miligy, I. M., Toss, M. S., Gorringe, K. L., Ellis, I. O., Green, A. R., & Rakha, E. A. (2022). Aurora Kinase A Is an Independent Predictor of Invasive Recurrence in Breast Ductal Carcinoma in situ. Pathobiology, 89(6), 382–392. https://doi.org/10.1159/000522244

Aurora Kinase A (AURKA/STK15) has a role in centrosome duplication and is a regulator of mitotic cell proliferation. It is over-expressed in breast cancer and other cancers, however; its role in ductal carcinoma in situ (DCIS) remains to be defined.... Read More about Aurora Kinase A Is an Independent Predictor of Invasive Recurrence in Breast Ductal Carcinoma in situ.

The characteristics and clinical significance of atypical mitosis in breast cancer (2022)
Journal Article
Lashen, A., Toss, M. S., Alsaleem, M., Green, A. R., Mongan, N. P., & Rakha, E. (2022). The characteristics and clinical significance of atypical mitosis in breast cancer. Modern Pathology, 35, 1341-1348. https://doi.org/10.1038/s41379-022-01080-0

Atypical mitosis is considered a feature of malignancy, however, its significance in breast cancer (BC) remains elusive. Here, we aimed to assess the clinical value of atypical mitoses in BC and to explore their underlying molecular features. Atypica... Read More about The characteristics and clinical significance of atypical mitosis in breast cancer.

Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer (2022)
Journal Article
Saunus, J. M., De Luca, X. M., Northwood, K., Raghavendra, A., Hasson, A., McCart Reed, A. E., …Lakhani, S. R. (2022). Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer. npj Breast Cancer, 8(1), Article 57. https://doi.org/10.1038/s41523-022-00425-x

Intratumoral heterogeneity is caused by genomic instability and phenotypic plasticity, but how these features co-evolve remains unclear. SOX10 is a neural crest stem cell (NCSC) specifier and candidate mediator of phenotypic plasticity in cancer. We... Read More about Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer.

Breast tumor microenvironment structures are associated with genomic features and clinical outcome (2022)
Journal Article
Danenberg, E., Bardwell, H., Zanotelli, V. R. T., Provenzano, E., Chin, S. F., Rueda, O. M., …Ali, H. R. (2022). Breast tumor microenvironment structures are associated with genomic features and clinical outcome. Nature Genetics, 54, 660–669. https://doi.org/10.1038/s41588-022-01041-y

The functions of the tumor microenvironment (TME) are orchestrated by precise spatial organization of specialized cells, yet little is known about the multicellular structures that form within the TME. Here we systematically mapped TME structures in... Read More about Breast tumor microenvironment structures are associated with genomic features and clinical outcome.

Standardization of the tumor-stroma ratio scoring method for breast cancer research (2022)
Journal Article
Hagenaars, S. C., Vangangelt, K. M. H., Van Pelt, G. W., Karancsi, Z., Tollenaar, R. A. E. M., Green, A. R., …Mesker, W. E. (2022). Standardization of the tumor-stroma ratio scoring method for breast cancer research. Breast Cancer Research and Treatment, 193, 545-553. https://doi.org/10.1007/s10549-022-06587-3

Purpose: The tumor-stroma ratio (TSR) has repeatedly proven to be correlated with patient outcomes in breast cancer using large retrospective cohorts. However, studies validating the TSR often show variability in methodology, thereby hampering compar... Read More about Standardization of the tumor-stroma ratio scoring method for breast cancer research.

Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer (2022)
Journal Article
Kurozumi, S., Kaira, K., Matsumoto, H., Kurosumi, M., Yokobori, T., Kanai, Y., …Horiguchi, J. (2022). Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer. Scientific Reports, 12(1), Article 2742. https://doi.org/10.1038/s41598-022-06615-8

L-type amino acid transporter 1 (LAT1), also referred to as SLC7A5, is believed to regulate tumor metabolism and be associated with tumor proliferation. In invasive breast cancer, we clinicopathologically investigated the utility of LAT1 expression.... Read More about Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer.

Upregulation of Cyclin B2 (CCNB2) in breast cancer contributes to the development of lymphovascular invasion (2022)
Journal Article
Aljohani, A. I., Toss, M. S., El-Sharawy, K. A., Mirza, S., Ball, G. R., Green, A. R., & Rakha, E. (2022). Upregulation of Cyclin B2 (CCNB2) in breast cancer contributes to the development of lymphovascular invasion. American Journal of Cancer Research, 12(2), 469-489

Lymphovascular invasion (LVI) is a key step in breast cancer (BC) metastasis. Targeting the molecular drivers of LVI can improve BC patients’ management. However, the underlying molecular mechanisms of LVI are complex and interconnected with various... Read More about Upregulation of Cyclin B2 (CCNB2) in breast cancer contributes to the development of lymphovascular invasion.

Ubiquitin-conjugating enzyme 2C (UBE2C) is a poor prognostic biomarker in invasive breast cancer (2022)
Journal Article
Kariri, Y., Toss, M. S., Alsaleem, M., Elsharawy, K. A., Joseph, C., Mongan, N. P., …Rakha, E. A. (2022). Ubiquitin-conjugating enzyme 2C (UBE2C) is a poor prognostic biomarker in invasive breast cancer. Breast Cancer Research and Treatment, 192(3), 529-539. https://doi.org/10.1007/s10549-022-06531-5

Background The Ubiquitin-conjugating enzyme 2C (UBE2C) is essential for the ubiquitin–proteasome system and is involved in cancer cell migration and apoptosis. This study aimed to determine the prognostic value of UBE2C in invasive breast cancer (BC... Read More about Ubiquitin-conjugating enzyme 2C (UBE2C) is a poor prognostic biomarker in invasive breast cancer.

Intra-operative assessment of sentinel lymph nodes for breast cancer surgery: An update (2021)
Journal Article
Barkur, S., Notingher, I., & Rakha, E. (2022). Intra-operative assessment of sentinel lymph nodes for breast cancer surgery: An update. Surgical Oncology, 40, Article 101678. https://doi.org/10.1016/j.suronc.2021.101678

Lymph node (LN) involvement is the strongest prognostic factor in operable breast cancer (BC). Therefore, accurate assessment of LN status is essential for management of BC patients. The introduction of sentinel LN approach reduced the need for exten... Read More about Intra-operative assessment of sentinel lymph nodes for breast cancer surgery: An update.

Untangling the clinicopathological significance of MRE11-RAD50-NBS1 complex in sporadic breast cancers (2021)
Journal Article
Alblihy, A., Shoqafi, A., Toss, M. S., Algethami, M., Harris, A. E., Jeyapalan, J. N., …Madhusudan, S. (2021). Untangling the clinicopathological significance of MRE11-RAD50-NBS1 complex in sporadic breast cancers. npj Breast Cancer, 7(1), 1-10. https://doi.org/10.1038/s41523-021-00350-5

The MRE11–RAD50–NBS1 (MRN) complex is critical for genomic stability. Although germline mutations in MRN may increase breast cancer susceptibility, such mutations are extremely rare. Here, we have conducted a comprehensive clinicopathological study o... Read More about Untangling the clinicopathological significance of MRE11-RAD50-NBS1 complex in sporadic breast cancers.

Assessment of proliferation in breast cancer: cell cycle or mitosis? An observational study (2021)
Journal Article
Lashen, A. G., Toss, M. S., Katayama, A., Gogna, R., Mongan, N. P., & Rakha, E. A. (2021). Assessment of proliferation in breast cancer: cell cycle or mitosis? An observational study. Histopathology, 79(6), 1087-1098. https://doi.org/10.1111/his.14542

Background and aims: Proliferation is an important indicator of breast cancer (BC) prognosis, but is assessed using different approaches. Not all cells in the cell cycle are committed to division. This study aimed to characterise quantitative differe... Read More about Assessment of proliferation in breast cancer: cell cycle or mitosis? An observational study.

Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer (2021)
Journal Article
Althobiti, M., El-Sharawy, K. A., Joseph, C., Aleskandarany, M., Toss, M. S., Green, A. R., & Rakha, E. A. (2021). Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer. Breast Cancer Research and Treatment, 189(3), 621-630. https://doi.org/10.1007/s10549-021-06336-y

Purpose The outcome of the luminal oestrogen receptor-positive (ER +) subtype of breast cancer (BC) is highly variable and patient stratification needs to be refined. We assessed the prognostic significance of oestrogen-regulated solute carrier fami... Read More about Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer.

The frequency and clinical significance of DNA polymerase beta (POLβ) expression in breast ductal carcinoma in situ (DCIS) (2021)
Journal Article
Al-Kawaz, A., Ali, R., Toss, M. S., Miligy, I. M., Mohammed, O. J., Green, A. R., …Rakha, E. A. (2021). The frequency and clinical significance of DNA polymerase beta (POLβ) expression in breast ductal carcinoma in situ (DCIS). Breast Cancer Research and Treatment, 190, 39-51. https://doi.org/10.1007/s10549-021-06357-7

Background: The prediction of clinical behaviour of breast ductal carcinoma in situ (DCIS) and its progression to invasive disease remains a challenge. Alterations of DNA damage repair mechanisms are associated with invasive breast cancer (BC). This... Read More about The frequency and clinical significance of DNA polymerase beta (POLβ) expression in breast ductal carcinoma in situ (DCIS).

The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer (2021)
Journal Article
Masisi, B. K., El Ansari, R., Alfarsi, L., Craze, M. L., Jewa, N., Oldfield, A., …Green, A. R. (2021). The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer. Cancers, 13(16), Article 3963. https://doi.org/10.3390/cancers13163963

Glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assess... Read More about The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer.

Ligase 1 is a predictor of platinum resistance and its blockade is synthetically lethal in XRCC1 deficient epithelial ovarian cancers (2021)
Journal Article
Ali, R., Alabdullah, M., Algethami, M., Alblihy, A., Miligy, I., Shoqafi, A., …Madhusudan, S. (2021). Ligase 1 is a predictor of platinum resistance and its blockade is synthetically lethal in XRCC1 deficient epithelial ovarian cancers. Theranostics, 11(17), 8350-8361. https://doi.org/10.7150/thno.51456

Rationale: The human ligases (LIG1, LIG3 and LIG4) are essential for the maintenance of genomic integrity by catalysing the formation of phosphodiester bonds between adjacent 5'-phosphoryl and 3'-hydroxyl termini at single and double strand breaks in... Read More about Ligase 1 is a predictor of platinum resistance and its blockade is synthetically lethal in XRCC1 deficient epithelial ovarian cancers.

SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in estrogen receptor-positive breast cancer (2021)
Journal Article
Alfarsi, L. H., Ansari, R. E., Craze, M. L., Mohammed, O. J., Masisi, B. K., Ellis, I. O., …Green, A. R. (2021). SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in estrogen receptor-positive breast cancer. Breast Cancer Research and Treatment, 189(2), 317-331. https://doi.org/10.1007/s10549-021-06298-1

Purpose: Identification of effective biomarkers for the benefit of endocrine treatment and understanding the molecular pathways that contribute to the development of resistance are of crucial importance to the management of luminal breast cancer. The... Read More about SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in estrogen receptor-positive breast cancer.

Adenomyoepithelioma of the breast: A proposal for classification (2021)
Journal Article
Rakha, E., Hoon Tan, P., Ellis, I., & Quinn, C. (2021). Adenomyoepithelioma of the breast: A proposal for classification. Histopathology, 79(4), 465-479. https://doi.org/10.1111/his.14380

Breast lesions with a prominent myoepithelial cell component constitute a heterogeneous group of benign and malignant neoplastic proliferations. These lesions are often dual epithelial‐myoepithelial but may be purely myoepithelial cell in nature. Ben... Read More about Adenomyoepithelioma of the breast: A proposal for classification.

The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ (2021)
Journal Article
Al-Kawaz, A., Miligy, I. M., Toss, M. S., Mohammed, O. J., Green, A. R., Madhusudan, S., & Rakha, E. A. (2021). The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ. Breast Cancer Research and Treatment, 188(1), 53-63. https://doi.org/10.1007/s10549-021-06271-y

Background Impaired DNA repair mechanism is one of the cancer hallmarks. Flap Endonuclease 1 (FEN1) is essential for genomic integrity. FEN1 has key roles during base excision repair (BER) and replication. We hypothesised a role for FEN1 in breast c... Read More about The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ.

PP1, PKA and DARPP-32 in breast cancer: a retrospective assessment of protein and mRNA expression (2021)
Journal Article
Saidy, B., Kotecha, S., Butler, A., Rakha, E., Ellis, I., Green, A., …Storr, S. (2021). PP1, PKA and DARPP-32 in breast cancer: a retrospective assessment of protein and mRNA expression. Journal of Cellular and Molecular Medicine, 25(11), 5015-5024. https://doi.org/10.1111/jcmm.16447

Cyclic-AMP dependent protein kinase A (PKA) and protein phosphatase 1 (PP1) are proteins involved in numerous essential signalling pathways that modulate physiological and pathological functions. Both PP1 and PKA can be inhibited by dopamine and cAMP... Read More about PP1, PKA and DARPP-32 in breast cancer: a retrospective assessment of protein and mRNA expression.

Diagnostic Concordance of Phyllodes Tumour of the Breast (2021)
Journal Article
Rakha, E., Mihai, R., Abbas, A., Bennett, R., Campora, M., Morena, P., …Ellis, I. (2021). Diagnostic Concordance of Phyllodes Tumour of the Breast. Histopathology, 79(4), 607-618. https://doi.org/10.1111/his.14397

Background: Phyllodes tumours (PT) are rare and distinct breast tumours, which span a morphological continuum. Classification into benign, borderline and malignant categories reflects their biology and clinical behaviour and is essential to guide man... Read More about Diagnostic Concordance of Phyllodes Tumour of the Breast.

RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer (2021)
Journal Article
Sanz-Moreno, A., Palomeras, S., Pedersen, K., Morancho, B., Pascual, T., Galván, P., …Gonzalez-Suarez, E. (2021). RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer. Breast Cancer Research, 23(1), Article 42. https://doi.org/10.1186/s13058-021-01390-2

Background Around 15–20% of primary breast cancers are characterized by HER2 protein overexpression and/or HER2 gene amplification. Despite the successful development of anti-HER2 drugs, intrinsic and acquired resistance represents a major hurdle. T... Read More about RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer.

Prognostic significance of heat shock protein 90AA1 (HSP90?) in invasive breast cancer (2021)
Journal Article
Alsaeed, S. A., Toss, M., Alsaleem, M., Aleskandarany, M., Joseph, C., Kurozumi, S., …Rakha, E. (2022). Prognostic significance of heat shock protein 90AA1 (HSP90α) in invasive breast cancer. Journal of Clinical Pathology, 75(4), 263-269. https://doi.org/10.1136/jclinpath-2020-207106

Aims: The mechanisms that drive breast cancer (BC) progression and poor outcome are not fully understood. The human heat shock protein 90 alpha family class A member 1 (HSP90?) encoded by the HSP90 'A1 gene has a vital role in cellular responses to s... Read More about Prognostic significance of heat shock protein 90AA1 (HSP90?) in invasive breast cancer.

Age-related biology of early-stage operable breast cancer and its impact on clinical outcome (2021)
Journal Article
Cheung, K. L., Ellis, I. O., Morgan, D. A., Rakha, E. A., Green, A. R., & Syed, B. M. (2021). Age-related biology of early-stage operable breast cancer and its impact on clinical outcome. Cancers, 13(6), Article 1417. https://doi.org/10.3390/cancers13061417

As age advances, breast cancer (BC) tends to change its biological characteristics. This study aimed to explore the natural progression of such changes. The study included 2383 women with clinically T0-2N0-1M0 BC, managed by primary surgery and optim... Read More about Age-related biology of early-stage operable breast cancer and its impact on clinical outcome.

Combined total internal reflection AF spectral-imaging and Raman spectroscopy for fast assessment of surgical margins during breast cancer surgery (2021)
Journal Article
Lizio, M. G., Liao, Z., Shipp, D. W., Boitor, R., Mihai, R., Sharp, J. S., …Notingher, I. (2021). Combined total internal reflection AF spectral-imaging and Raman spectroscopy for fast assessment of surgical margins during breast cancer surgery. Biomedical Optics Express, 12(2), 940-954. https://doi.org/10.1364/boe.411648

The standard treatment for breast cancer is surgical removal mainly through breast conserving surgey (BCS). We developed a new technique based on auto-fluorescence (AF) spectral imaging and Raman spectroscopy for fast intraoperative assessment of exc... Read More about Combined total internal reflection AF spectral-imaging and Raman spectroscopy for fast assessment of surgical margins during breast cancer surgery.

RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers (2020)
Journal Article
Alblihy, A., Alabdullah, M. L., Toss, M. S., Algethami, M., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2020). RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers. Molecular Biomedicine, 1(1), Article 19. https://doi.org/10.1186/s43556-020-00023-y

Intrinsic or acquired resistance seriously limits the use of platinating agents in advanced epithelial ovarian cancers. Increased DNA repair capacity is a key route to platinum resistance. RAD50 is a critical component of the MRN complex, a ‘first re... Read More about RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers.

High tissue inhibitor of matrix-metalloproteinase 2 expression correlates with poor prognosis in breast cancer (2020)
Conference Proceeding
Heyman, T., Joseph, C., Craze, M., Green, A., Nolan, C., Rueda, O., …Mukherjee, A. (2020). High tissue inhibitor of matrix-metalloproteinase 2 expression correlates with poor prognosis in breast cancer

Background & objectives TIMP2, tissue inhibitor of matrix-metalloproteinase 2, inhibits the matrix-metalloproteinase, MMP2, but may activate pro-MMP2. Hence its correlation with prognosis in breast cancer (BC) is contradictory. This study investigat... Read More about High tissue inhibitor of matrix-metalloproteinase 2 expression correlates with poor prognosis in breast cancer.

Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer (2020)
Journal Article
Elsharawy, K. A., Althobiti, M., Mohammed, O. J., Aljohani, A. I., Toss, M. S., Green, A. R., & Rakha, E. (2021). Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer. Breast Cancer Research and Treatment, 185(3), 615-627. https://doi.org/10.1007/s10549-020-05999-3

Purpose Nucleolar protein 10 (NOP10) is required for ribosome biogenesis and telomere maintenance and plays a key role in carcinogenesis. This study aims to evaluate the clinical and prognostic significance of NOP10 in breast cancer (BC). Methods... Read More about Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer.

The prognostic significance of Interferon Stimulated Gene 15 (ISG15) in invasive breast cancer (2020)
Journal Article
Kariri, Y., Alsaleem, M., Joseph, C., Alsaeed, S., Aljohani, A., Shiino, S., …Rakha, E. A. (2021). The prognostic significance of Interferon Stimulated Gene 15 (ISG15) in invasive breast cancer. Breast Cancer Research and Treatment, 185(2), 293–305. https://doi.org/10.1007/s10549-020-05955-1

Background Lymphovascular invasion (LVI) is a prognostic factor in early-stage invasive breast cancer (BC). Through bioinformatics, data analyses of multiple BC cohorts revealed the positive association between interferon-stimulated gene 15 (ISG15... Read More about The prognostic significance of Interferon Stimulated Gene 15 (ISG15) in invasive breast cancer.

Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer (2020)
Journal Article
Morotti, M., Zois, C. E., El-Ansari, R., Craze, M. L., Rakha, E. A., Fan, S., …Harris, A. L. (2021). Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer. British Journal of Cancer, 124(2), 494-505. https://doi.org/10.1038/s41416-020-01113-y

The nucleolar related protein Dyskerin pseudouridine 1 synthase 1 (DKC1) predicts poor prognosis in breast cancer (2020)
Journal Article
Elsharawy, K. A., Mohammed, O. J., Aleskandarany, M. A., Hyder, A., El-Gammal, H. L., -Dobara, A., …Rakha, E. A. (2020). The nucleolar related protein Dyskerin pseudouridine 1 synthase 1 (DKC1) predicts poor prognosis in breast cancer. British Journal of Cancer, 123, 1543–1552. https://doi.org/10.1038/s41416-020-01045-7

Background Hypertrophy of the nucleolus is a distinctive cytological feature of malignant cells and corresponds to aggressive behaviour. This study aimed to identify the key gene associated with nucleolar prominence (NP) in breast cancer (BC) and... Read More about The nucleolar related protein Dyskerin pseudouridine 1 synthase 1 (DKC1) predicts poor prognosis in breast cancer.

Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets (2020)
Journal Article
Kurozumi, S., Alsaleem, M., Monteiro, C. J., Bhardwaj, K., Joosten, S. E., Fujii, T., …Johnston, S. J. (2020). Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets. Breast Cancer Research, 22, Article 85. https://doi.org/10.1186/s13058-020-01324-4

© 2020 The Author(s). Background: Invasive lobular carcinoma (ILC) accounts for 10-15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable... Read More about Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets.

The clinical significance of oestrogen receptor expression in breast ductal carcinoma in situ (2020)
Journal Article
Miligy, I. M., Toss, M. S., Shiino, S., Oni, G., Syed, B. M., Khout, H., …Rakha, E. A. (2020). The clinical significance of oestrogen receptor expression in breast ductal carcinoma in situ. British Journal of Cancer, 123(10), 1513-1520. https://doi.org/10.1038/s41416-020-1023-3

Background: Oestrogen receptor (ER) in invasive breast cancer (BC) predicts response to endocrine therapy (ET) and provides prognostic value. In this study, we investigated the value of ER expression in ductal carcinoma in situ (DCIS) in terms of out... Read More about The clinical significance of oestrogen receptor expression in breast ductal carcinoma in situ.

Werner Syndrome Protein Expression in Breast Cancer (2020)
Journal Article
Savva, C., Sadiq, M., Sheikh, O., Karim, S., Trivedi, S., Green, A. R., …Arora, A. (2021). Werner Syndrome Protein Expression in Breast Cancer. Clinical Breast Cancer, 21(1), 57-73.E7. https://doi.org/10.1016/j.clbc.2020.07.013

Introduction Werner protein (WRN) plays an important role in DNA repair, replication, transcription, and consequently genomic stability via its DNA-helicase and exonuclease activity. Loss of function of WRN is associated with Werner syndrome (WS), w... Read More about Werner Syndrome Protein Expression in Breast Cancer.

IL6/STAT3 Signaling Hijacks Estrogen Receptor ? Enhancers to Drive Breast Cancer Metastasis (2020)
Journal Article
Siersbaek, R., Scabia, V., Nagarajan, S., Chernukhin, I., Papachristou, E. K., Broome, R., …Carroll, J. S. (2020). IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis. Cancer Cell, 38(3), 412-423.e9. https://doi.org/10.1016/j.ccell.2020.06.007

The cytokine interleukin-6 (IL6) and its downstream effector STAT3 constitute a key oncogenic pathway, which has been thought to be functionally connected to estrogen receptor ? (ER) in breast cancer. We demonstrate that IL6/STAT3 signaling drives me... Read More about IL6/STAT3 Signaling Hijacks Estrogen Receptor ? Enhancers to Drive Breast Cancer Metastasis.

Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype (2020)
Journal Article
Kariri, Y. A., Aleskandarany, M. A., Joseph, C., Toss, M. S., Kurozumi, S., Mohammed, O. J., …Rakha, E. A. (2020). Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype. Pathobiology, 87, 218–231. https://doi.org/10.1159/000508337

Lymphovascular invasion (LVI) is associated with poor outcome in breast cancer (BC); however, its underlying mechanisms remain ill-defined. LVI in BC develops through complex molecular pathways involving not only the interplay with the surrounding mi... Read More about Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype.

Feasibility of integrated high?wavenumber Raman imaging and fingerprint Raman spectroscopy for fast margin assessment in breast cancer surgery (2020)
Journal Article
Liao, Z., Lizio, M. G., Corden, C., Khout, H., Rakha, E., & Notingher, I. (2020). Feasibility of integrated high?wavenumber Raman imaging and fingerprint Raman spectroscopy for fast margin assessment in breast cancer surgery. Journal of Raman Spectroscopy, 51(10), 1986-1995. https://doi.org/10.1002/jrs.5937

Intraoperative assessment of surgical margins remains one of the main challenges in cancer surgery. Raman spectroscopy can detect cancer cells with high accuracy, but it is time‐consuming. In this paper, we investigated a selective‐sampling Raman spe... Read More about Feasibility of integrated high?wavenumber Raman imaging and fingerprint Raman spectroscopy for fast margin assessment in breast cancer surgery.

The prognostic significance of BMI1 expression in invasive breast cancer is dependent on its molecular subtypes (2020)
Journal Article
Althobiti, M., Muftah, A. A., Aleskandarany, M. A., Joseph, C., Toss, M. S., Green, A., & Rakha, E. (2020). The prognostic significance of BMI1 expression in invasive breast cancer is dependent on its molecular subtypes. Breast Cancer Research and Treatment, 182, 581–589. https://doi.org/10.1007/s10549-020-05719-x

Purpose: BMI-1, which is a major component of the polycomb group complex 1 is an essential epigenetic repressor of multiple regulatory genes and has been identified as a cancer stem cell (CSC) marker in several cancers. However, its role in breast c... Read More about The prognostic significance of BMI1 expression in invasive breast cancer is dependent on its molecular subtypes.

Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival (2020)
Journal Article
Joseph, C., Alsaleem, M., Orah, N., Narasimha, P. L., Miligy, I. M., Kurozumi, S., …Rakha, E. A. (2020). Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival. Breast Cancer Research and Treatment, 182, 267–282. https://doi.org/10.1007/s10549-020-05670-x

Purpose: MMP9 is a matricellular protein associated with extracellular matrix (ECM) remodelling, that promotes tumour progression, and modulates the activity of cell adhesion molecules and cytokines. This study aims to assess the prognostic value of... Read More about Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival.

PPFIA1 expression associates with poor response to endocrine treatment in luminal breast cancer (2020)
Journal Article
Alfarsi, L. H., El Ansari, R., Craze, M. L., Masisi, B. K., Ellis, I. O., Rakha, E. A., & Green, A. R. (2020). PPFIA1 expression associates with poor response to endocrine treatment in luminal breast cancer. BMC Cancer, 20(1), https://doi.org/10.1186/s12885-020-06939-6

Background PPFIA1 is an important regulator of cell migration and invasion, regulating focal adhesion signalling and disassembly. PPFIA1 is frequently amplified in breast cancer, and recent functional studies indicate that PPFIA1 is an important pro... Read More about PPFIA1 expression associates with poor response to endocrine treatment in luminal breast cancer.

A novel prognostic two-gene signature for triple negative breast cancer (2020)
Journal Article
Alsaleem, M. A., Ball, G., Toss, M. S., Raafat, S., Aleskandarany, M., Joseph, C., …Rakha, E. (2020). A novel prognostic two-gene signature for triple negative breast cancer. Modern Pathology, 33, 2208–2220. https://doi.org/10.1038/s41379-020-0563-7

The absence of a robust risk stratification tool for triple negative breast cancer (TNBC) underlies imprecise and non-selective treatment of these patients with cytotoxic chemotherapy. This study aimed to interrogate transcriptomes of TNBC resected s... Read More about A novel prognostic two-gene signature for triple negative breast cancer.

The prognostic significance of ALDH1A1 expression in early invasive breast cancer (2020)
Journal Article
Althobiti, M., El Ansari, R., Aleskandarany, M., Joseph, C., Toss, M. S., Green, A. R., & Rakha, E. A. (2020). The prognostic significance of ALDH1A1 expression in early invasive breast cancer. Histopathology, 77(3), 437-448. https://doi.org/10.1111/his.14129

Aims: Aldehyde dehydrogenase family 1 member A1 (ALDH1A1)is reportedly a key ALDH isozyme linked to the cancer stem cells (CSC) of many solid tumours, where it is involved in self-renewal, differentiation and self-protection. In this study, the progn... Read More about The prognostic significance of ALDH1A1 expression in early invasive breast cancer.

Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer (2020)
Journal Article
Aljohani, A. I., Joseph, C., Kurozumi, S., Mohammed, O. J., Miligy, I. M., Green, A. R., & Rakha, E. (2020). Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer. Breast Cancer Research and Treatment, 181(3), 541-551. https://doi.org/10.1007/s10549-020-05646-x

Background: Breast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early stage BC can help understand the risk of metastasis and guide treatment dec... Read More about Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer.

The solute carrier SLC7A8 is a marker of favourable prognosis in ER-positive low proliferative invasive breast cancer (2020)
Journal Article
Ansari, R., Craze, M. L., Alfarsi, L., Masisi, B. K., Ellis, I. O., Rakha, E. A., & Green, A. R. (2020). The solute carrier SLC7A8 is a marker of favourable prognosis in ER-positive low proliferative invasive breast cancer. Breast Cancer Research and Treatment, 181(1), 1-12. https://doi.org/10.1007/s10549-020-05586-6

Purpose: Breast cancer (BC) is a heterogeneous disease consisting of various subtypes, with different prognostic and therapeutic outcomes. The amino acid transporter, SLC7A8, is over expressed in estrogen receptor positive BC. However the consequenc... Read More about The solute carrier SLC7A8 is a marker of favourable prognosis in ER-positive low proliferative invasive breast cancer.

The prognostic significance of immune microenvironment in breast ductal carcinoma in situ (2020)
Journal Article
Toss, M. S., Abidi, A., Lesche, D., Joseph, C., Mahale, S., Saunders, H., …Rakha, E. A. (2020). The prognostic significance of immune microenvironment in breast ductal carcinoma in situ. British Journal of Cancer, 122, 1496–1506. https://doi.org/10.1038/s41416-020-0797-7

Background The role of different subtypes of tumour infiltrating lymphocytes (TILs) in breast ductal carcinoma in situ (DCIS) is still poorly defined. This study aimed to assess the prognostic significance of B and T lymphocytes and immune checkpo... Read More about The prognostic significance of immune microenvironment in breast ductal carcinoma in situ.

The genetic architecture of breast papillary lesions as a predictor of progression to carcinoma (2020)
Journal Article
Thio, N., Kader, T., Elder, K., Zethoven, M., Semple, T., Hill, P., …Gorringe, K. L. (2020). The genetic architecture of breast papillary lesions as a predictor of progression to carcinoma. npj Breast Cancer, 6, Article 9. https://doi.org/10.1038/s41523-020-0150-6

Intra-ductal papillomas (IDP) are challenging breast findings because of their variable risk of progression to malignancy. The molecular events driving IDP development and genomic features of malignant progression are poorly understood. In this study... Read More about The genetic architecture of breast papillary lesions as a predictor of progression to carcinoma.

PIK3C? expression by fibroblasts promotes triple-negative breast cancer progression (2020)
Journal Article
Huang, P., Gagliano, T., Shah, K., Gargani, S., Lao, L., Alsaleem, M., …Giamas, G. (2020). PIK3Cδ expression by fibroblasts promotes triple-negative breast cancer progression. Journal of Clinical Investigation, 130(6), 3188-3204. https://doi.org/10.1172/jci128313

As there is growing evidence for the tumor microenvironment’s (TME) role in tumorigenesis, we investigated the role of fibroblast-expressed kinases in triple negative breast cancer (TNBC). Using a high-throughput kinome screen combined with 3D invasi... Read More about PIK3C? expression by fibroblasts promotes triple-negative breast cancer progression.

Combined HER3-EGFR score in triple-negative breast cancer provides prognostic and predictive significance superior to individual biomarkers (2020)
Journal Article
Janssen, E. A., Ogden, A., Bhattarai, S., Sahoo, B., Mongan, N. P., Alsaleem, M., …Aneja, R. (2020). Combined HER3-EGFR score in triple-negative breast cancer provides prognostic and predictive significance superior to individual biomarkers. Scientific Reports, 10(1), Article 3009. https://doi.org/10.1038/s41598-020-59514-1

© 2020, The Author(s). Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) have been investigated as triple-negative breast cancer (TNBC) biomarkers. Reduced EGFR levels can be compensated by increases in HER3;... Read More about Combined HER3-EGFR score in triple-negative breast cancer provides prognostic and predictive significance superior to individual biomarkers.

Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer (2020)
Journal Article
Alfarsi, L. H., El-Ansari, R., Craze, M. L., Masisi, B. K., Mohammed, O. J., Rakha, E. A., …Green, A. R. (2020). Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer. International Journal of Molecular Sciences, 21(4), Article 1407. https://doi.org/10.3390/ijms21041407

The majority of breast cancers are oestrogen receptor positive (ER+) and are subject to endocrine therapy however, an unpredictable subgroup of patients will develop resistance to endocrine therapy. SLC7A5/SLC3A2 complex is a major route for the tran... Read More about Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer.

XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib (2020)
Journal Article
Ali, R., Alblihy, A., Toss, M. S., Algethami, M., Al Sunni, R., Green, A. R., …Madhusudan, S. (2020). XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib. Therapeutic Advances in Medical Oncology, 12, 175883592097420. https://doi.org/10.1177/1758835920974201

Background: PARP inhibitor (PARPi) monotherapy is a new strategy in BRCA germ-line deficient triple negative breast cancer (TNBC). However, not all patients respond, and the development of resistance limits the use of PARPi monotherapy. Therefore, th... Read More about XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib.

The prognostic value of the tumor–stroma ratio is most discriminative in patients with grade III or triple‐negative breast cancer (2020)
Journal Article
Vangangelt, K. M., Green, A. R., Heemskerk, I. (. F., Cohen, D., Van Pelt, G. W., Sobral-Leite, M., …Mesker, W. E. (2020). The prognostic value of the tumor–stroma ratio is most discriminative in patients with grade III or triple‐negative breast cancer. International Journal of Cancer, 146(8), 2296-2304. https://doi.org/10.1002/ijc.32857

The tumor-stroma ratio (TSR) was evaluated as a promising parameter for breast cancer prognostication in clinically relevant subgroups of patients. The TSR was assessed on hematoxylin and eosin stained tissue slides of 1794 breast cancer patients fro... Read More about The prognostic value of the tumor–stroma ratio is most discriminative in patients with grade III or triple‐negative breast cancer.

Enhanced glutamine uptake influences composition of immune cell infiltrates in breast cancer (2019)
Journal Article
Ansari, R. E., Craze, M. L., Althobiti, M., Alfarsi, L., Ellis, I. O., Rakha, E. A., & Green, A. R. (2019). Enhanced glutamine uptake influences composition of immune cell infiltrates in breast cancer. British Journal of Cancer, 122(1), 94–101. https://doi.org/10.1038/s41416-019-0626-z

Background: Cancer cells must alter their metabolism to support proliferation. Immune evasion also plays a role in supporting tumour progression. This study aimed to find whether enhanced glutamine uptake in breast cancer (BC) can derive the existenc... Read More about Enhanced glutamine uptake influences composition of immune cell infiltrates in breast cancer.

Clinicopathological Characteristics of Basal-like Breast Cancer (BLBC): a Comparative Study between Egyptian and British Patients (2019)
Journal Article
Mohammed, R. A. A., El-Deek, H. E. M., Aleskandarany, M. A., Green, A. R., Ellis, I. O., & Rakha, E. A. (2019). Clinicopathological Characteristics of Basal-like Breast Cancer (BLBC): a Comparative Study between Egyptian and British Patients. Egyptian Journal of Pathology, 16(1), 115-122. https://doi.org/10.4103/EGJP.EGJP_15_19

Background and aims: Clinicopathological features of Basal-like Breast Cancer (BLBC) in African American women have been extensively studied. Comparatively, less is known about these tumors in patients from countries in the North African region. The... Read More about Clinicopathological Characteristics of Basal-like Breast Cancer (BLBC): a Comparative Study between Egyptian and British Patients.

Dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP-32) and survival in breast cancer: a retrospective analysis of protein and mRNA expression (2019)
Journal Article
Kotecha, S., Lebot, M. N., Sukkarn, B., Ball, G., Moseley, P. M., Chan, S. Y., …Storr, S. J. (2019). Dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP-32) and survival in breast cancer: a retrospective analysis of protein and mRNA expression. Scientific Reports, 9, 1-11. https://doi.org/10.1038/s41598-019-53529-z

Dopamine and cAMP regulated phosphoprotein 32?kDa (DARPP-32) also known as phosphoprotein phosphatase-1 regulatory subunit 1B and encoded by the PPP1R1B gene is an inhibitor of protein phosphatase-1 and protein kinase A. DARPP-32 is expressed in a wi... Read More about Dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP-32) and survival in breast cancer: a retrospective analysis of protein and mRNA expression.

Prognostic Significance of Nucleolar Assessment in Invasive Breast Cancer (2019)
Journal Article
Elsharawy, K. A., Toss, M. S., Raaft, S. R., Ball, G., Green, A. R., Aleskandarany, M. A., …Rakha, E. A. (2020). Prognostic Significance of Nucleolar Assessment in Invasive Breast Cancer. Histopathology, 76(5), 671-684. https://doi.org/10.1111/his.14036

Aims: Nucleolar morphometric features have a potential role in the assessment of aggressiveness of many cancers. However, the role of nucleoli in invasive breast cancer (IBC) is still unclear. This study aimed to investigate the optimal scoring metho... Read More about Prognostic Significance of Nucleolar Assessment in Invasive Breast Cancer.

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer (2019)
Journal Article
Kurozumi, S., Alsaeed, S., Orah, N., Miligy, I. M., Joseph, C., Aljohani, A., …Rakha, E. A. (2020). Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer. Breast Cancer Research and Treatment, 179, 557–564. https://doi.org/10.1007/s10549-019-05488-2

PURPOSE: The epithelial–mesenchymal transition (EMT) plays a key role in breast cancer progression and metastasis. Lipocalin 2 (LCN2) is involved in the regulation of EMT. The aim of this study was to investigate the clinicopathological significance... Read More about Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer.

Prognostic Significance of KN Motif and Ankyrin Repeat Domains 1 (KANK1) in Invasive Breast Cancer (2019)
Journal Article
Kariri, Y. A., Joseph, C., Kurozumi, S., Toss, M. S., Alsaleem, M., Raafat, S., …Rakha, E. A. (2020). Prognostic Significance of KN Motif and Ankyrin Repeat Domains 1 (KANK1) in Invasive Breast Cancer. Breast Cancer Research and Treatment, 179(2), 349–357. https://doi.org/10.1007/s10549-019-05466-8

Background: KN Motif and Ankyrin Repeat Domains 1 (KANK1) plays an important role in cytoskeleton maintenance and contributes to the regulation of cell proliferation, adhesion and apoptosis. KANK1 is involved in progression of a variety of solid tumo... Read More about Prognostic Significance of KN Motif and Ankyrin Repeat Domains 1 (KANK1) in Invasive Breast Cancer.

ATM Regulated PTEN Degradation Is XIAP E3 Ubiquitin Ligase Mediated in p85? Deficient Cancer Cells and Influence Platinum Sensitivity (2019)
Journal Article
Ali, R., Alabdullah, M., Miligy, I., Normatova, M., Babaei-Jadidi, R., S. Nateri, A., …Madhusudan, S. (2019). ATM Regulated PTEN Degradation Is XIAP E3 Ubiquitin Ligase Mediated in p85α Deficient Cancer Cells and Influence Platinum Sensitivity. Cells, 8(10), Article 1271. https://doi.org/10.3390/cells8101271

Ataxia-telegiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), and p85? are key tumour suppressors. Whether ATM regulates PTEN expression and influence platinum sensitivity is unknown. We generated ATM knockdowns (KD) and CRISPR knock out... Read More about ATM Regulated PTEN Degradation Is XIAP E3 Ubiquitin Ligase Mediated in p85? Deficient Cancer Cells and Influence Platinum Sensitivity.

The prognostic significance of wild type isocitrate dehydrogenase 2 (IDH2) in breast cancer (2019)
Journal Article
Aljohani, A. I., Toss, M. S., Kurozumi, S., Joseph, C., Aleskandarany, M. A., Miligy, I. M., …Rakha, E. (2020). The prognostic significance of wild type isocitrate dehydrogenase 2 (IDH2) in breast cancer. Breast Cancer Research and Treatment, 179(1), 79–90. https://doi.org/10.1007/s10549-019-05459-7

Background: Lymphovascular invasion (LVI) is a prerequisite step in breast cancer (BC) metastasis. We have previously identified wild type isocitrate dehydrogenase 2 (IDH2) as a key putative driver of LVI. Thus, we explored the prognostic significanc... Read More about The prognostic significance of wild type isocitrate dehydrogenase 2 (IDH2) in breast cancer.

The Role Of Glutaminase In Cancer (2019)
Journal Article
Masisi, B., El Ansari, R., Alfarsi, L., Rakha, E., Green, A., & Craze, M. (2020). The Role Of Glutaminase In Cancer. Histopathology, 76(4), 498-508. https://doi.org/10.1111/his.14014

Increased glutamine metabolism (glutaminolysis) is a hallmark of cancer and is recognised as a key metabolic change in cancer cells. As a heterogeneous disease with different morpholog- ical and molecular subtypes and response to therapy, breast canc... Read More about The Role Of Glutaminase In Cancer.

Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer (2019)
Journal Article
Joseph, C., Al-Izzi, S., Alsaleem, M., Kurozumi, S., Toss, M., Arshad, M., …Rakha, E. A. (2019). Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer. British Journal of Cancer, 121(9), 776-785. https://doi.org/10.1038/s41416-019-0589-0

© 2019, The Author(s), under exclusive licence to Cancer Research UK. Background: Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic signi... Read More about Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer.

The intra-tumoral stroma in patients with breast cancer increases with age (2019)
Journal Article
Vangangelt, K. M. H., Kramer, C. J. H., Bastiaannet, E., Putter, H., Cohen, D., van Pelt, G. W., …Mesker, W. E. (2020). The intra-tumoral stroma in patients with breast cancer increases with age. Breast Cancer Research and Treatment, 179(1), 37–45. https://doi.org/10.1007/s10549-019-05422-6

Purpose The tumor microenvironment in older patients is subject to changes. The tumor-stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoral stroma and to evaluate the prognostic value of the TSR in older patients with br... Read More about The intra-tumoral stroma in patients with breast cancer increases with age.

CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy (2019)
Journal Article
Alfarsi, L., Ansari, R. E., Craze, M. L., Toss, M. S., Masisi, B., Ellis, I. O., …Green, A. R. (2019). CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy. Breast Cancer Research and Treatment, 178(3), 535-544. https://doi.org/10.1007/s10549-019-05420-8

Purpose Endocrine therapy is the standard treatment for oestrogen receptor positive (ER+) breast cancer. Despite its efficacy, around half of patients will develop resistance to this treatment and eventually relapse. Identification of effective and... Read More about CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy.

Prognostic significance of cathepsin V (CTSV/CTSL2) in breast ductal carcinoma in situ (2019)
Journal Article
Toss, M. S., Miligy, I. M., Gorringe, K. L., Mittal, K., Green, A. R., Aneja, R., …Rakha, E. A. (2020). Prognostic significance of cathepsin V (CTSV/CTSL2) in breast ductal carcinoma in situ. Journal of Clinical Pathology, 73(2), 76-82. https://doi.org/10.1136/jclinpath-2019-205939

Aims: Cathepsin V (CTSV/CTSL2) is a lysosomal cystine proteinase and plays a role in extracellular matrix degradation. It is associated with poor prognosis in invasive breast cancer (IBC), but its role in breast ductal carcinoma in situ (DCIS) remain... Read More about Prognostic significance of cathepsin V (CTSV/CTSL2) in breast ductal carcinoma in situ.

Machine learning-based prediction of breast cancer growth rate in-vivo (2019)
Journal Article
Bhattarai, S., Klimov, S., Aleskandarany, M. A., Burrell, H., Wormall, A., Green, A. R., …Aneja, R. (2019). Machine learning-based prediction of breast cancer growth rate in-vivo. British Journal of Cancer, 121, 497–504. https://doi.org/10.1038/s41416-019-0539-x

Background Determining the rate of breast cancer (BC) growth in vivo, which can predict prognosis, has remained elusive despite its relevance for treatment, screening recommendations and medicolegal practice. We developed a model that predicts the r... Read More about Machine learning-based prediction of breast cancer growth rate in-vivo.

Whole?exome sequencing and RNA sequencing analyses of acinic cell carcinomas of the breast (2019)
Journal Article
Beca, F., Lee, S. S., Pareja, F., da Cruz Paula, A., Selenica, P., Ferrando, L., …Reis‐Filho, J. S. (2019). Whole‐exome sequencing and RNA sequencing analyses of acinic cell carcinomas of the breast. Histopathology, 75(6), 931-937. https://doi.org/10.1111/his.13962

Aims Acinic cell carcinoma of the breast (ACC) is a rare histologic form of triple?negative breast cancer (TNBC). Despite its unique histology, targeted sequencing analysis has failed to identify recurrent genetic alterations other than those found... Read More about Whole?exome sequencing and RNA sequencing analyses of acinic cell carcinomas of the breast.

A whole slide image-based machine learning approach to predict ductal carcinoma in situ (DCIS) recurrence risk (2019)
Journal Article
Klimov, S., Miligy, I. M., Gertych, A., Jiang, Y., Toss, M. S., Rida, P., …Aneja, R. (2019). A whole slide image-based machine learning approach to predict ductal carcinoma in situ (DCIS) recurrence risk. Breast Cancer Research, 21(1), Article 83. https://doi.org/10.1186/s13058-019-1165-5

© 2019 The Author(s). Background: Breast ductal carcinoma in situ (DCIS) represent approximately 20% of screen-detected breast cancers. The overall risk for DCIS patients treated with breast-conserving surgery stems almost exclusively from local recu... Read More about A whole slide image-based machine learning approach to predict ductal carcinoma in situ (DCIS) recurrence risk.

Surgical management of ductal carcinoma in situ of the breast: A large retrospective study from a single institution (2019)
Journal Article
Miligy, I. M., Toss, M. S., Khout, H., Hc, B., Ellis, I. O., Green, A. R., …Rakha, E. (2019). Surgical management of ductal carcinoma in situ of the breast: A large retrospective study from a single institution. Breast Journal, 25(6), 1143-1153. https://doi.org/10.1111/tbj.13425

Background: Management of breast ductal carcinoma in situ (DCIS) has various approaches with distinct institutional specific practice. Here, we review DCIS management in a single institution with emphasise on re-operation rates and outcome. Methods:... Read More about Surgical management of ductal carcinoma in situ of the breast: A large retrospective study from a single institution.

Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study (2019)
Journal Article
Bhattarai, S., Klimov, S., Mittal, K., Krishnamurti, U., Li, B., Oprea-Ilies, G., …Aneja, R. (2019). Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study. Cancers, 11(7), Article 995. https://doi.org/10.3390/cancers11070995

Background: Androgen Receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR’s prognostic role in TNBC are putting its usefulness in question. Some st... Read More about Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.

Collagen (XI) alpha-1 chain (COL11A1) is an independent prognostic factor in breast ductal carcinoma in situ (2019)
Journal Article
Toss, M. S., Miligy, I. M., Gorringe, K. L., Aleskandarany, M. A., Alkawaz, A., Mittal, K., …Rakha, E. A. (2019). Collagen (XI) alpha-1 chain (COL11A1) is an independent prognostic factor in breast ductal carcinoma in situ. Modern Pathology,

Collagen11A1 (COL11A1) is a fibrillary type collagen constituting a minor component of the extracellular matrix and plays role in tissue tensile strength. Overexpression of COL11A1 expression is associated with aggressive behavior and poor outcome in... Read More about Collagen (XI) alpha-1 chain (COL11A1) is an independent prognostic factor in breast ductal carcinoma in situ.

Geometric characteristics of collagen have independent prognostic significance in breast ductal carcinoma in situ: an image analysis study (2019)
Journal Article
Toss, M. S., Miligy, I. M., Gorringe, K. L., Alkawaz, A., Mittal, K., Aneja, R., …Rakha, E. A. (2019). Geometric characteristics of collagen have independent prognostic significance in breast ductal carcinoma in situ: an image analysis study. Modern Pathology, 32(10), 1473-1485. https://doi.org/10.1038/s41379-019-0296-7

Collagen plays a key role in normal and malignant tissue homeostasis. While the prognostic significance of collagen fibre remodeling in invasive breast cancer has been studied, its role in ductal carcinoma in situ (DCIS) remains poorly defined. Using... Read More about Geometric characteristics of collagen have independent prognostic significance in breast ductal carcinoma in situ: an image analysis study.

A Key Genomic Subtype Associated with Lymphovascular Invasion in Invasive Breast Cancer (2019)
Journal Article
Kurozumi, S., Joseph, C., Alsaeed, S., Kariri, Y., Aljohani, A., Raafat, S., …Rakha, E. A. (2019). A Key Genomic Subtype Associated with Lymphovascular Invasion in Invasive Breast Cancer. British Journal of Cancer, 120(12), 1129–1136. https://doi.org/10.1038/s41416-019-0486-6

Background: Lymphovascular invasion (LVI) is associated with the development of metastasis in invasive breast cancer (BC). However, the complex molecular mechanisms of LVI, which overlap with other oncogenic pathways, remain unclear. This study, usin... Read More about A Key Genomic Subtype Associated with Lymphovascular Invasion in Invasive Breast Cancer.

Combining clustering and classification ensembles: A novel pipeline to identify breast cancer profiles (2019)
Journal Article
Agrawal, U., Soria, D., Wagner, C., Garibaldi, J., Ellis, I. O., Bartlett, J. M. S., …Green, A. R. (2019). Combining clustering and classification ensembles: A novel pipeline to identify breast cancer profiles. Artificial Intelligence in Medicine, 97, 27-37. https://doi.org/10.1016/j.artmed.2019.05.002

Breast Cancer is one of the most common causes of cancer death in women, representing a very complex disease with varied molecular alterations. To assist breast cancer prognosis, the classification of patients into biological groups is of great signi... Read More about Combining clustering and classification ensembles: A novel pipeline to identify breast cancer profiles.

The clinical and biological significance of HER2 over-expression in breast ductal carcinoma in situ: a large study from a single institution (2019)
Journal Article
Miligy, I. M., Toss, M. S., Gorringe, K. L., Lee, A. H., Ellis, I. O., Green, A. R., & Rakha, E. (2019). The clinical and biological significance of HER2 over-expression in breast ductal carcinoma in situ: a large study from a single institution. British Journal of Cancer, 120(11), 1075-1082. https://doi.org/10.1038/s41416-019-0436-3

© 2019, Cancer Research UK. Background: Previous studies have reported up to 50% of ductal carcinoma in situ (DCIS), is HER2 positive, but the frequency of HER2-positive invasive breast cancer (IBC) is lower. The aim of this study is to characterise... Read More about The clinical and biological significance of HER2 over-expression in breast ductal carcinoma in situ: a large study from a single institution.

Metadherin: A Therapeutic Target in Multiple Cancers (2019)
Journal Article
Dhiman, G., Srivastava, N., Goyal, M., Rakha, E., Lothion-Roy, J., Mongan, N. P., …Baranwal, M. (2019). Metadherin: A Therapeutic Target in Multiple Cancers. Frontiers in Oncology, 9, Article 349. https://doi.org/10.3389/fonc.2019.00349

Altered expression of many genes and proteins is essential for cancer development and progression. Recently, the affected expression of metadherin (MTDH), also known as AEG-1 (Astrocyte Elevated Gene 1) and Lyric, has been implicated in various aspec... Read More about Metadherin: A Therapeutic Target in Multiple Cancers.

Utility of Ankyrin 3 as a Prognostic Marker in Androgen-Receptor-Positive Breast Cancer Running Title: Prognostic Value of ANK3 in AR-Positive Breast Cancer (2019)
Journal Article
Kurozumi, S., Joseph, C., Raafat, S., Sonbul, S., Kariri, Y., Alsaeed, S., …Rakha, E. A. (2019). Utility of Ankyrin 3 as a Prognostic Marker in Androgen-Receptor-Positive Breast Cancer Running Title: Prognostic Value of ANK3 in AR-Positive Breast Cancer. Breast Cancer Research and Treatment, 176(1), 63–73. https://doi.org/10.1007/s10549-019-05216-w

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Purpose: Androgen receptor (AR) and AR signaling pathways are thought to play a role in breast cancer (BC) and are potentially related to treatment responses and outcomes. Ankyrin... Read More about Utility of Ankyrin 3 as a Prognostic Marker in Androgen-Receptor-Positive Breast Cancer Running Title: Prognostic Value of ANK3 in AR-Positive Breast Cancer.

Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma (2019)
Journal Article
Kader, T., Hill, P., Zethoven, M., Goode, D. L., Elder, K., Thio, N., …Gorringe, K. L. (2019). Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma. Journal of Pathology, 248(3), 326-338. https://doi.org/10.1002/path.5262

The current model for breast cancer progression proposes independent “low‐grade (LG) like” and “high‐grade (HG) like” pathways but lacks a known precursor to HG cancer. We applied low coverage whole genome sequencing to atypical ductal hyperplasia (A... Read More about Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma.

SHON expression predicts response and relapse risk of breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment (2019)
Journal Article
Abdel-Fatah, T. M., Broom, R. J., Lu, J., Moseley, P. M., Huang, B., Li, L., …Liu, D. (2019). SHON expression predicts response and relapse risk of breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment. British Journal of Cancer, 120(7), 728–745. https://doi.org/10.1038/s41416-019-0405-x

BACKGROUND: SHON nuclear expression (SHON-Nuc+) was previously reported to predict clinical outcomes to tamoxifen therapy in ER?+ breast cancer (BC). Herein we determined if SHON expression detected by specific monoclonal antibodies could provide a m... Read More about SHON expression predicts response and relapse risk of breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment.

The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts (2019)
Journal Article
Rida, P. C. G., Alsaleem, M., Toss, M. S., Joseph, C., Aleskandarany, M., Kurozumi, S., …Rakha, E. A. (2019). The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts. Modern Pathology, 32(7), 967-976. https://doi.org/10.1038/s41379-019-0209-9

© 2019, United States & Canadian Academy of Pathology. E-cadherin is a tumor suppressor gene in invasive lobular breast cancer. However, a proportion of high-grade ductal carcinoma shows reduced/loss of E-cadherin. In this study, we assessed the un... Read More about The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts.

Clinicopathological significance of ataxia-telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3 related (ATR) kinase in MYC overexpressed breast cancers (2019)
Journal Article
Savva, C., De Souza, K., Ali, R., Rakha, E. A., Green, A. R., & Madhusudan, S. (2019). Clinicopathological significance of ataxia-telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3 related (ATR) kinase in MYC overexpressed breast cancers. Breast Cancer Research and Treatment, 175(1), 105–115. https://doi.org/10.1007/s10549-018-05113-8

Purpose: MYC transcription factor has critical roles in cell growth, proliferation, metabolism, differentiation, transformation and angiogenesis. MYC overexpression is seen in about 15% of breast cancers and linked to aggressive phenotypes. MYC overe... Read More about Clinicopathological significance of ataxia-telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3 related (ATR) kinase in MYC overexpressed breast cancers.

The prognostic significance of lysosomal protective protein (Cathepsin A) in breast ductal carcinoma in situ (2019)
Journal Article
Toss, M. S., Miligy, I. M., Haj-Ahmad, R., Gorringe, K. L., AlKawaz, A., Mittal, K., …Rakha, E. A. (2019). The prognostic significance of lysosomal protective protein (Cathepsin A) in breast ductal carcinoma in situ. Histopathology, 74(7), 1025-1035. https://doi.org/10.1111/his.13835

Background: Cathepsin A (CTSA) is a key regulatory enzyme for galactoside metabolism. Additionally, it has a distinct proteolytic activity and plays a role in tumour progression. CTSA is differentially expressed at the mRNA level between br... Read More about The prognostic significance of lysosomal protective protein (Cathepsin A) in breast ductal carcinoma in situ.

The combined expression of solute carriers is associated with a poor prognosis in highly proliferative ER+ breast cancer (2019)
Journal Article
El-Ansari, R., El Ansari, R., Craze, M. L., Alfarsi, L., Soria, D., Diez-Rodriguez, M., …Green, A. R. (2019). The combined expression of solute carriers is associated with a poor prognosis in highly proliferative ER+ breast cancer. Breast Cancer Research and Treatment, 175(1), 27-38. https://doi.org/10.1007/s10549-018-05111-w

Purpose: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity, and patient outcome. Glutamine availability for growth and progression of BC is important in several BC sub... Read More about The combined expression of solute carriers is associated with a poor prognosis in highly proliferative ER+ breast cancer.

Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas (2019)
Journal Article
Pareja, F., Geyer, F. C., Brown, D. N., Sebastião, A. P. M., Gularte-Mérida, R., Li, A., …Reis-Filho, J. S. (2019). Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas. npj Breast Cancer, 5, Article 6 (2019). https://doi.org/10.1038/s41523-018-0101-7

Breast adenomyoepitheliomas (AMEs) are rare epithelial-myoepithelial neoplasms that may occasionally produce myxochondroid matrix, akin to pleomorphic adenomas (PAs). Regardless of their anatomic location, PAs often harbor rearrangements involving HM... Read More about Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas.

Expression of Lamin A/C in early-stage breast cancer and its prognostic value (2019)
Journal Article
Alhudiri, I., Nolan, C., Ellis, I., Elzagheid, A., Rakha, E., Green, A., & Chapman, C. (2019). Expression of Lamin A/C in early-stage breast cancer and its prognostic value. Breast Cancer Research and Treatment, 174(3), 661–668. https://doi.org/10.1007/s10549-018-05092-w

Purpose: Lamins A/C, a major component of the nuclear lamina, plays key roles in maintaining nuclear integrity, regulation of gene expression, cell proliferation and apoptosis. Reduced lamin A/C expression in cancer has been reported to be a sign of... Read More about Expression of Lamin A/C in early-stage breast cancer and its prognostic value.

Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer (2018)
Journal Article
Joseph, C., Arshad, M., Kurozomi, S., Althobiti, M., Miligy, I. M., Al-Izzi, S., …Rakha, E. A. (2019). Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer. Breast Cancer Research and Treatment, 174(2), 387-399. https://doi.org/10.1007/s10549-018-05085-9

Purpose CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic... Read More about Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer.

Connexin 43 is an independent predictor of patient outcome in breast cancer patients (2018)
Journal Article
Chasampalioti, M., Green, A. R., Ellis, I. O., Rakha, E. A., Jackson, A. M., Spendlove, I., & Ramage, J. M. (2019). Connexin 43 is an independent predictor of patient outcome in breast cancer patients. Breast Cancer Research and Treatment, 174(1), 93-102. https://doi.org/10.1007/s10549-018-5063-9

Purpose Gap junctions are specialized membrane structures that form channels between adjacent cells allowing cell communication. Gap junctions and specifically Connexin 43 (Cx43) are down-regulated in cancer; however, there are contrasting reports... Read More about Connexin 43 is an independent predictor of patient outcome in breast cancer patients.

Glutamate dehydrogenase (GLUD1) expression in breast cancer (2018)
Journal Article
Craze, M. L., El-Ansari, R., Aleskandarany, M. A., Cheng, K. W., Al-Farsi, L., Masisi, B., …Green, A. R. (2019). Glutamate dehydrogenase (GLUD1) expression in breast cancer. Breast Cancer Research and Treatment, 174(1), 79–91. https://doi.org/10.1007/s10549-018-5060-z

Dysregulated cellular metabolism is regarded as one of the hallmarks of cancer with some tumours utilising the glutamine metabolism pathway for their sustained proliferation and survival. Glutamate dehydrogenase (GLUD1) is a key enzyme in glutaminoly... Read More about Glutamate dehydrogenase (GLUD1) expression in breast cancer.

Legumain is an independent predictor for invasive recurrence in breast ductal carcinoma in situ (2018)
Journal Article
Toss, M. S., Miligy, I. M., Gorringe, K. L., McCaffrey, L., Alkawaz, A., Abidi, A., …Rakha, E. A. (2019). Legumain is an independent predictor for invasive recurrence in breast ductal carcinoma in situ. Modern Pathology, 32, 639-649. https://doi.org/10.1038/s41379-018-0180-x

© 2018, United States & Canadian Academy of Pathology. Legumain is a proteolytic enzyme that plays a role in the regulation of cell proliferation in invasive breast cancer. Studies evaluating its role in ductal carcinoma in situ (DCIS) are lacking.... Read More about Legumain is an independent predictor for invasive recurrence in breast ductal carcinoma in situ.

Prolyl-4-hydroxylase ? subunit 2 (P4HA2) expression is a predictor of poor outcome in breast ductal carcinoma in situ (DCIS) (2018)
Journal Article
Toss, M. S., Miligy, I. M., Gorringe, K. L., Alkawaz, A., Khout, H., Ellis, I. O., …Rakha, E. (2018). Prolyl-4-hydroxylase Α subunit 2 (P4HA2) expression is a predictor of poor outcome in breast ductal carcinoma in situ (DCIS). British Journal of Cancer, 119(12), 1518-1526. https://doi.org/10.1038/s41416-018-0337-x

© 2018, Cancer Research UK. Background: Extracellular matrix (ECM) plays a crucial role in tumour behaviour. Prolyl-4-hydroxlase-A2 (P4HA2) is a key enzyme in ECM remodelling. This study aims to evaluate the prognostic significance of P4HA2 in breast... Read More about Prolyl-4-hydroxylase ? subunit 2 (P4HA2) expression is a predictor of poor outcome in breast ductal carcinoma in situ (DCIS).

Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair (2018)
Journal Article
Johnston, S. J., Ahmad, D., Aleskandarany, M. A., Kurozumi, S., Nolan, C. C., Diez-Rodriguez, M., …Rakha, E. A. (2018). Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair. BMC Cancer, 18, Article 1027. https://doi.org/10.1186/s12885-018-4924-2

Breast tumours resembling the tall cell variant of thyroid papillary carcinoma: are they part of the papillary carcinoma spectrum or a distinct entity? (2018)
Journal Article
Toss, M., Billingham, K., Egbuniwe, I., Moreno, F., Abass, A., & Rakha, E. (2018). Breast tumours resembling the tall cell variant of thyroid papillary carcinoma: are they part of the papillary carcinoma spectrum or a distinct entity?. Pathobiology, 1-9. https://doi.org/10.1159/000490416

Background: Papillary tumours of the breast are diagnostically challenging lesions and represent a wide spectrum of diseases from papilloma to invasive papillary carcinoma. A rare subtype of breast papillary tumour resembling the tall cell variant of... Read More about Breast tumours resembling the tall cell variant of thyroid papillary carcinoma: are they part of the papillary carcinoma spectrum or a distinct entity?.

Kinesin family member-18A (KIF18A) is a predictive biomarker of poor benefit from endocrine therapy in early ER+?breast cancer (2018)
Journal Article
Alfarsi, L. H., Elansari, R., Toss, M. S., Diez-Rodriguez, M., Nolan, C. C., Ellis, I. O., …Green, A. R. (2018). Kinesin family member-18A (KIF18A) is a predictive biomarker of poor benefit from endocrine therapy in early ER+ breast cancer. Breast Cancer Research and Treatment, https://doi.org/10.1007/s10549-018-4978-5

PURPOSE: Identification of effective and reliable biomarkers that could be used to predict the efficacy of endocrine therapy is of crucial importance to the management of oestrogen receptor positive (ER+) breast cancer (BC). KIF18A, a key regulator o... Read More about Kinesin family member-18A (KIF18A) is a predictive biomarker of poor benefit from endocrine therapy in early ER+?breast cancer.

Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention (2018)
Journal Article
Ali, R., Al-Kawaz, A., Toss, M. S., Green, A. R., Miligy, I. M., Mesquita, K. A., …Madhusudan, S. (2018). Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention. Cancer Research, 78(24), 6818-6827. https://doi.org/10.1158/0008-5472.CAN-18-0633

© 2018 American Association for Cancer Research. Targeting PARP1 for synthetic lethality is a new strategy for breast cancers harboring germline mutations in BRCA. However, these mutations are rare, and reactivation of BRCA-mediated pathways may resu... Read More about Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention.

Loss-of-function mutations in ATP6AP1 and ATP6AP2 in granular cell tumors (2018)
Journal Article
Pareja, F., Brandes, A. H., Basili, T., Selenica, P., Geyer, F. C., Fan, D., …Reis-Filho, J. S. (2018). Loss-of-function mutations in ATP6AP1 and ATP6AP2 in granular cell tumors. Nature Communications, 9, Article 3533. https://doi.org/10.1038/s41467-018-05886-y

Granular cell tumors (GCTs) are rare tumors that can arise in multiple anatomical locations, and are characterized by abundant intracytoplasmic granules. The genetic drivers of GCTs are currently unknown. Here, we apply whole-exome sequencing and tar... Read More about Loss-of-function mutations in ATP6AP1 and ATP6AP2 in granular cell tumors.

A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal (2018)
Journal Article
Rindi, G., Klimstra, D. S., Abedi-Ardekani, B., Asa, S. L., Bosman, F. T., Brambilla, E., …Cree, I. A. (2018). A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Modern Pathology, 31(12), 1770-1786. https://doi.org/10.1038/s41379-018-0110-y

© 2018, United States & Canadian Academy of Pathology. The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical lo... Read More about A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal.

The role of PIP5K1?/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1? inhibitor (2018)
Journal Article
Sarwar, M., Syed Khaja, A. S., Aleskandarany, M., Karlsson, R., Althobiti, M., Ødum, N., …Persson, J. L. (2019). The role of PIP5K1α/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1α inhibitor. Oncogene, 38(3), 375-389. https://doi.org/10.1038/s41388-018-0438-2

© 2018, The Author(s). Despite recent improvement in adjuvant therapies, triple-negative, and ER + subtypes of breast cancer (BC) with metastatic potentials remain the leading cause of BC-related deaths. We investigated the role of phosphatidylinosi... Read More about The role of PIP5K1?/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1? inhibitor.

Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer (2018)
Journal Article
Kurozumi, S., Joseph, C., Sonbul, S., Aleskandarany, M. A., Pigera, M., Alsaleem, M., …Rakha, E. A. (2018). Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer. Breast Cancer Research and Treatment, 172(1), 61–68. https://doi.org/10.1007/s10549-018-4891-y

BACKGROUND: Ras association and pleckstrin homology domains 1 (RAPH1) is involved in cytoskeleton regulation and re-epithelialisation in invasive carcinoma and therefore may play a key role in carcinogenesis and metastasis. We herein investigated the... Read More about Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer.

The spectrum of triple-negative breast disease: high- and low-grade lesions (2018)
Journal Article
Geyer, F. C., Pareja, F., Weigelt, B., Rakha, E., Ellis, I. O., Schnitt, S. J., & Reis-Filho, J. S. (2018). The spectrum of triple-negative breast disease: high- and low-grade lesions. American Journal of Pathology, 187(10), 2139-2151. https://doi.org/10.1016/j.ajpath.2017.03.016

Triple-negative breast cancer is viewed clinically as an aggressive subgroup of breast cancer. In fact, most triple-negative breast cancers are poor-prognosis tumors with a complex genomic landscape. However, triple-negative disease is vastly heterog... Read More about The spectrum of triple-negative breast disease: high- and low-grade lesions.

Impact of breast cancer grade discordance on prediction of outcome (2018)
Journal Article
Rakha, E. A., Aleskandarany, M. A., Toss, M. S., Mongan, N., El-Sayed, M. E., Green, A. R., …Dalton, L. W. (in press). Impact of breast cancer grade discordance on prediction of outcome. Histopathology, https://doi.org/10.1111/his.13709

BACKGROUND: Histological grade is an independent prognostic variable in breast cancer (BC). Previous concordance studies of BC grade have reported moderate levels of agreement; a typical finding in morphological assessment of biological variables. Th... Read More about Impact of breast cancer grade discordance on prediction of outcome.

Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery (2018)
Journal Article
Shipp, D. W., Rakha, E. A., Koloydenko, A. A., Macmillan, R. D., Ellis, I. O., & Notingher, I. (2018). Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery. Breast Cancer Research, 20, https://doi.org/10.1186/s13058-018-1002-2

Background: In over 20% of breast conserving operations, postoperative pathological assessment of the excised tissue reveals positive margins, requiring additional surgery. Current techniques for intra-operative assessment of tumor margins are insuff... Read More about Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery.

Breast cancer intratumour heterogeneity: current status and clinical implications (2018)
Journal Article
Joseph, C., Papadaki, A., Althobiti, M., Alsaleem, M., Aleskandarany, M. A., & Rakha, E. A. (2018). Breast cancer intratumour heterogeneity: current status and clinical implications. Histopathology, 73(5), (717-731). doi:10.1111/his.13642. ISSN 0309-0167

Breast cancer (BC) is a heterogeneous disease that varies in presentation, morphological features, behaviour, and response to therapy. High?throughput molecular profiling studies have revolutionised our understanding of BC heterogeneity, and have dem... Read More about Breast cancer intratumour heterogeneity: current status and clinical implications.

The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response (2018)
Journal Article
Barone, G., Arora, A., Ganesh, A., Abdel-Fatah, T., Moseley, P., Ali, R., …Collis, S. J. (2018). The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response. Oncotarget, 9, 29508-29524. https://doi.org/10.18632/oncotarget.25686

Background: Cyclin-Dependent Kinases (CDKs) are established anti-cancer drug targets and a new generation of CDK inhibitors are providing clinical benefits to a sub-set of breast cancer patients. We have recently shown that human CDK18 promotes effic... Read More about The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response.

Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ (2018)
Journal Article
Miligy, I. M., Gorringe, K. L., Toss, M. S., Al-Kawaz, A., Simpson, P., Diez-Rodriguez, M., …Rakha, E. (2018). Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ. Modern Pathology, 31(12), 1807-1815. https://doi.org/10.1038/s41379-018-0086-7

Current clinicopathological parameters are useful predictors of breast ductal carcinoma in situ behaviour, but they are insufficient to define high risk patients for disease progression precisely. Thioredoxin interacting protein (TXNIP) is a key play... Read More about Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ.

Saccharomyces cerevisiae-like 1 (SEC14L1) is a prognostic factor in breast cancer associated with lymphovascular invasion (2018)
Journal Article
Sonbul, S. N., Aleskandarany, M. A., Kurozumi, S., Joseph, C., Toss, M. S., Diez-Rodriguez, M., …Rakha, E. A. (in press). Saccharomyces cerevisiae-like 1 (SEC14L1) is a prognostic factor in breast cancer associated with lymphovascular invasion. Modern Pathology, https://doi.org/10.1038/s41379-018-0092-9

Lymphovascular invasion is strongly related to breast cancer metastasis. However, the underlying mechanisms of lymphovascular invasion and its driver molecules in breast cancer remain to be defined. In this study, we explore differential expression o... Read More about Saccharomyces cerevisiae-like 1 (SEC14L1) is a prognostic factor in breast cancer associated with lymphovascular invasion.

Heterogeneity of Tumour Infiltrating Lymphocytes (TILs) in breast cancer and its prognostic significance (2018)
Journal Article
Althobiti, M., Aleskandarany, M. A., Joseph, C., Toss, M., Mongan, N., Diez-Rodriguez, M., …Rakha, E. A. (2018). Heterogeneity of Tumour Infiltrating Lymphocytes (TILs) in breast cancer and its prognostic significance. Histopathology, 73(6), 887-896. https://doi.org/10.1111/his.13695

Background: Tumour-infiltrating lymphocytes (TILs) in breast cancer (BC) confer prognostic and predictive information. This study aims to assess the spatial and temporal heterogeneity of TILs in BC and its relationship with immune cell subtypes. Met... Read More about Heterogeneity of Tumour Infiltrating Lymphocytes (TILs) in breast cancer and its prognostic significance.

Inhibition of her2 increases jagged1-dependent breast cancer stem cells: Role for membrane jagged1 (2018)
Journal Article
Shah, D., Wyatt, D., Baker, A., Simms, P., Peiffer, D. S., Fernandez, M. L., …Osipo, C. (2018). Inhibition of her2 increases jagged1-dependent breast cancer stem cells: Role for membrane jagged1. Clinical Cancer Research, 24(18), 4566-4578. https://doi.org/10.1158/1078-0432.CCR-17-1952

© 2018 American Association for Cancer Research. Purpose: HER2-positive breast cancer is driven by cells possessing stem-like properties of self-renewal and differentiation, referred to as cancer stem cells (CSC). CSCs are implicated in radiotherapy... Read More about Inhibition of her2 increases jagged1-dependent breast cancer stem cells: Role for membrane jagged1.

Solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (solid papillary carcinomas with reverse polarity) harbour recurrent mutations affecting IDH2 and PIK3CA: a validation cohort (2018)
Journal Article
Lozada, J. R., Basili, T., Pareja, F., Alemar, B., Paula, A. D. C., Gularte-Merida, R., …Geyer, F. C. (2018). Solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (solid papillary carcinomas with reverse polarity) harbour recurrent mutations affecting IDH2 and PIK3CA: a validation cohort. Histopathology, 73(2), 339-344. https://doi.org/10.1111/his.13522

Aims: Solid papillary breast carcinoma resembling the tall cell variant of papillary thyroid neoplasms (BPTC), also known as solid papillary carcinomawith reverse polarity, is a rare histological type of breast cancer that resembles morphologically t... Read More about Solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (solid papillary carcinomas with reverse polarity) harbour recurrent mutations affecting IDH2 and PIK3CA: a validation cohort.

Panoptic overview of triple-negative breast cancer in Nigeria: current challenges and promising global initiatives (2018)
Journal Article
Wright, N., Rida, P., Rakha, E., Agboola, A., & Aneja, R. (2018). Panoptic overview of triple-negative breast cancer in Nigeria: current challenges and promising global initiatives. Journal of Global Oncology, 1-20. https://doi.org/10.1200/jgo.17.00116

Purpose Triple-negative breast cancer (TNBC) is the most deadly form of breast cancer (BC) today. TNBC treatment is fraught with challenges because of the extensive interpatient heterogeneity in clinical behavior and scarcity of stratifying biomar... Read More about Panoptic overview of triple-negative breast cancer in Nigeria: current challenges and promising global initiatives.

Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas (2018)
Journal Article
Geyer, F. C., Li, A., Papanastasiou, A. D., Smith, A., Selenica, P., Burke, K. A., …Reis-Filho, J. S. (2018). Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas. Nature Communications, 9, Article 1816. https://doi.org/10.1038/s41467-018-04128-5

Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, of which a subset will progress to invasive or metastatic cancer. We sought to define the genomic landscape of adenomyoepitheliomas. Massivel... Read More about Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas.

Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients (2018)
Journal Article
Martin, S. G., Lebot, M. N., Sukkarn, B., Ball, G., Green, A. R., Rakha, E. A., …Storr, S. J. (2018). Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients. Oncotarget, 9(40), 25946-25956. https://doi.org/10.18632/oncotarget.25408

G protein-coupled oestrogen receptor 1 (GPER), also called G protein-coupled receptor 30 (GPR30), is attracting considerable attention for its potential role in breast cancer development and progression. Activation by oestrogen (17β-oestradiol; E2) i... Read More about Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients.

Atypical ductal hyperplasia: update on diagnosis, management, and molecular landscape (2018)
Journal Article
Kader, T., Hill, P., Rakha, E. A., Campbell, I. G., & Gorringe, K. L. (2018). Atypical ductal hyperplasia: update on diagnosis, management, and molecular landscape. Breast Cancer Research, 20, 1-11. https://doi.org/10.1186/s13058-018-0967-1

Background Atypical ductal hyperplasia (ADH) is a common diagnosis in the mammographic era and a significant clinical problem with wide variation in diagnosis and treatment. After a diagnosis of ADH on biopsy a proportion are upgraded to carcinoma u... Read More about Atypical ductal hyperplasia: update on diagnosis, management, and molecular landscape.

Tumour heterogeneity of breast cancer: from morphology to personalised medicine (2018)
Journal Article
Aleskandarany, M. A., Vandenberghe, M. E., Marchiò, C., Ellis, I. O., Sapino, A., & Rakha, E. A. (2018). Tumour heterogeneity of breast cancer: from morphology to personalised medicine. Pathobiology, 85(1-2), 23-34. https://doi.org/10.1159/000477851

Breast cancer (BC) displays striking clinical, morphological, and behavioural diversity within a single tumour and between tumours. Currently, mounting evidence indicates that the morphological heterogeneity of BC reflects an underlying spectrum of g... Read More about Tumour heterogeneity of breast cancer: from morphology to personalised medicine.

Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis (2018)
Journal Article
Kurozumi, S., Joseph, C., Sonbul, S., Gorringe, K. L., Pigera, M., Aleskandarany, M. A., …Rakha, E. A. (in press). Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis. Breast Cancer Research and Treatment, 170(3), https://doi.org/10.1007/s10549-018-4777-z

Background: The functions of many proteins are tightly regulated with a complex array of cellular functions including ubiquitination. In cancer cells, aberrant ubiquitination may promote the activity of oncogenic pathways with subsequent tumour progr... Read More about Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis.

Current issues with luminal subtype classification in terms of prediction of benefit from endocrine therapy in early breast cancer (2018)
Journal Article
Alfarsi, L., Johnston, S., Liu, D., Rakha, E., & Green, A. (in press). Current issues with luminal subtype classification in terms of prediction of benefit from endocrine therapy in early breast cancer. Histopathology, https://doi.org/10.1111/his.13523

Endocrine therapy for oestrogen receptor?positive (ER+) breast cancer (BC) is arguably the most successful targeted cancer therapy to date. Nevertheless, resistance to endocrine therapy still occurs in a significant proportion of patients, limiting i... Read More about Current issues with luminal subtype classification in terms of prediction of benefit from endocrine therapy in early breast cancer.

Diagnostic concordance of reporting lymphovascular invasion in breast cancer (2018)
Journal Article
Rakha, E. A., Abbas, A., Pinto Ahumada, P., ElSayed, M. E., Colman, D., Pinder, S. E., & Ellis, I. O. (2018). Diagnostic concordance of reporting lymphovascular invasion in breast cancer. Journal of Clinical Pathology, 71(9), (802-805). doi:10.1136/jclinpath-2017-204981. ISSN 0021-9746

Aims: This study aims to assess the diagnostic agreement of lymphovascular invasion (LVI) in invasive breast cancer (BC). Methods: Data on LVI were collected from the UK National Health Service Breast Screening Programme pathology external quality... Read More about Diagnostic concordance of reporting lymphovascular invasion in breast cancer.

Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes (2018)
Journal Article
Joseph, C., Macnamara, O., Craze, M., Russell, R., Provenzano, E., Nolan, C. C., …Mukherjee, A. (in press). Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes. British Journal of Cancer, https://doi.org/10.1038/s41416-018-0041-x

Background: Mediator complex (MED) proteins have a key role in transcriptional regulation, some interacting with the oestrogen receptor (ER). Interrogation of the METABRIC cohort suggested that MED7 may regulate lymphovascular invasion (LVI). Thus ME... Read More about Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes.

The amino acid transporter SLC7A5 confers a poor prognosis in the highly proliferative breast cancer subtypes and is a key therapeutic target in luminal B tumours (2018)
Journal Article
El Ansari, R., Craze, M. L., Miligy, I., Diez-Rodriguez, M., Nolan, C. C., Ellis, I. O., …Green, A. R. (in press). The amino acid transporter SLC7A5 confers a poor prognosis in the highly proliferative breast cancer subtypes and is a key therapeutic target in luminal B tumours. Breast Cancer Research, 20(21), https://doi.org/10.1186/s13058-018-0946-6

Background: Breast cancer (BC) is a heterogeneous disease characterised by variant biology and patient outcome. The amino acid transporter, SLC7A5, plays a role in BC although its impact on patient outcome in different BC subtypes remains to be valid... Read More about The amino acid transporter SLC7A5 confers a poor prognosis in the highly proliferative breast cancer subtypes and is a key therapeutic target in luminal B tumours.

Prognostic significance of tumor-infiltrating lymphocytes in ductal carcinoma in situ of the breast (2018)
Journal Article
Toss, M. S., Miligy, I., Al-Kawaz, A., Alsleem, M., Khout, H., Rida, P. C., …Rakha, E. (in press). Prognostic significance of tumor-infiltrating lymphocytes in ductal carcinoma in situ of the breast. Modern Pathology, https://doi.org/10.1038/s41379-018-0040-8

Tumor-infiltrating lymphocytes (TILs) provide prognostic value in invasive breast cancer and guidelines for their assessment have been published. This study aims to evaluate: (a) methods of TILs assessment, and (b) their prognostic significance in br... Read More about Prognostic significance of tumor-infiltrating lymphocytes in ductal carcinoma in situ of the breast.

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes (2018)
Journal Article
El Ansari, R., Craze, M. L., Diez-Rodriguez, M., Nolan, C. C., Ellis, I. O., Rakha, E. A., & Green, A. R. (2018). The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes. British Journal of Cancer, 118(8), 1115-1122. https://doi.org/10.1038/s41416-018-0038-5

Background: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emp... Read More about The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes.

Breast cancer histologic grading using digital microscopy: concordance and outcome association (2018)
Journal Article
Rakha, E. A., Aleskandarani, M., Toss, M. S., Green, A. R., Ball, G., Ellis, I. O., & Dalton, L. W. (2018). Breast cancer histologic grading using digital microscopy: concordance and outcome association. Journal of Clinical Pathology, 71(8), 680-686. doi:10.1136/jclinpath-2017-204979

AIMS: Virtual microscopy utilising digital whole slide imaging (WSI) is increasingly used in breast pathology. Histologic grade is one of the strongest prognostic factors in breast cancer (BC). This study aims at investigating the agreement between B... Read More about Breast cancer histologic grading using digital microscopy: concordance and outcome association.

Loss of the nuclear pool of ubiquitin ligase CHIP/STUB1 in breast cancer unleashes the MZF1-cathepsin pro-oncogenic program (2018)
Journal Article
Luan, H., Mohapatra, B. C., Bielecki, T. A., Mushtaq, I., Mirza, S., Jennings, T. A., …Band, H. (2018). Loss of the nuclear pool of ubiquitin ligase CHIP/STUB1 in breast cancer unleashes the MZF1-cathepsin pro-oncogenic program. Cancer Research, 78(10), 2524-2535. https://doi.org/10.1158/0008-5472.CAN-16-2140

CHIP/STUB1 ubiquitin ligase is a negative co-chaperone for HSP90/HSC70, and its expression is reduced or lost in several cancers, including breast cancer. Using an extensive and well-annotated breast cancer tissue collection, we identified the loss o... Read More about Loss of the nuclear pool of ubiquitin ligase CHIP/STUB1 in breast cancer unleashes the MZF1-cathepsin pro-oncogenic program.

Immune infiltration in invasive lobular breast cancer (2018)
Journal Article
Desmedt, C., Salgado, R., Fornili, M., Pruneri, G., Gert Van den Eynden, G., Zoppoli, G., …Sotiriou, C. (2018). Immune infiltration in invasive lobular breast cancer. JNCI: Journal of the National Cancer Institute, 110(7), 768–776. https://doi.org/10.1093/jnci/djx268

Background: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels and composition of tumor infiltrating lymphocytes... Read More about Immune infiltration in invasive lobular breast cancer.

First international TNBC conference meeting report (2018)
Journal Article
Rida, P., Ogden, A., Ellis, I. O., Varga, Z., Wolff, A. C., Traina, T. A., …Aneja, R. (2018). First international TNBC conference meeting report. Breast Cancer Research and Treatment, 169(3), 407-412. https://doi.org/10.1007/s10549-018-4692-3

Recently, Georgia State University’s Centennial Hall was the premier location for the 2017 International Conference on Triple Negative Breast Cancer (TNBC): Illuminating Actionable Biology, which was held from Sept. 18 to 20, 2017, in Atlanta, USA. T... Read More about First international TNBC conference meeting report.

The significance of tumour microarchitectural features in breast cancer prognosis: a digital image analysis (2018)
Journal Article
Roxanis, I., Colling, R., Kartsonaki, C., Green, A., & Rakha, E. (2018). The significance of tumour microarchitectural features in breast cancer prognosis: a digital image analysis. Breast Cancer Research, 20(11), https://doi.org/10.1186/s13058-018-0934-x

BACKGROUND: As only a minor portion of the information present in histological sections is accessible by eye, recognition and quantification of complex patterns and relationships among constituents relies on digital image analysis. In this study, our... Read More about The significance of tumour microarchitectural features in breast cancer prognosis: a digital image analysis.

Targeting ataxia telangiectasia mutated and Rad3 related kinase (ATR) in PTEN deficient breast cancers for personalized therapy (2018)
Journal Article
Al-Subhi, N., Ali, R., Abdel-Fatah, T., Moseley, P. M., Chan, S. Y., Green, A. R., …Madhusudan, S. (2018). Targeting ataxia telangiectasia mutated and Rad3 related kinase (ATR) in PTEN deficient breast cancers for personalized therapy. Breast Cancer Research and Treatment, 169(2), 277–286. https://doi.org/10.1007/s10549-018-4683-4

Purpose: PTEN, a negative regulator of PI3K signaling, is involved in DNA repair. ATR is a key sensor of DNA damage and replication stress. We evaluated whether ATR signaling has clinical significance and could be targeted by synthetic lethality in P... Read More about Targeting ataxia telangiectasia mutated and Rad3 related kinase (ATR) in PTEN deficient breast cancers for personalized therapy.

BQ323636.1, a novel splice variant to NCOR2, as a predictor for tamoxifen resistant breast cancer (2018)
Journal Article
Gong, C., Man, E. P., Tsoi, H., Lee, T. K., Paul, L., Mak, S., …Khoo, U. (2018). BQ323636.1, a novel splice variant to NCOR2, as a predictor for tamoxifen resistant breast cancer. Clinical Cancer Research, 24(15), 3681-3691. https://doi.org/10.1158/1078-0432.CCR-17-2259

Purpose: Adjuvant tamoxifen treatment revolutionized the management of estrogen receptor (ER) positive breast cancers to prevent cancer recurrence; however drug resistance compromises its clinical efficacy. The mechanisms underlying tamoxifen resista... Read More about BQ323636.1, a novel splice variant to NCOR2, as a predictor for tamoxifen resistant breast cancer.

High nuclear MSK1 is associated with longer survival in breast cancer patients (2018)
Journal Article
Pu, X., Storr, S. J., Ahmad, N., Rakha, E., Green, A. R., Ellis, I. O., & Martin, S. G. (2018). High nuclear MSK1 is associated with longer survival in breast cancer patients. Journal of Cancer Research and Clinical Oncology, 144(3), https://doi.org/10.1007/s00432-018-2579-7

Purpose: Mitogen- and stress- activated kinases (MSKs) are important substrates of the mitogen-activated protein kinase (MAPK)-activated protein kinase family. MSK1 and MSK2 are both nuclear serine/threonine protein kinases, with MSK1 being suggested... Read More about High nuclear MSK1 is associated with longer survival in breast cancer patients.

IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients (2017)
Journal Article
Ahmad, N., Ammar, A., Storr, S. J., Green, A. R., Rakha, E., Ellis, I., & Martin, S. G. (2018). IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients. Cancer Immunology, Immunotherapy, 67(4), https://doi.org/10.1007/s00262-017-2106-8

Macrophage-associated cytokines play an important role in cancer metastasis however the functions of Interleukins (IL) 6 and 10 in breast cancer (BC) progression and metastasis are not clear. In this study the roles of IL-6/IL-10 in regulating vascul... Read More about IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients.

Invasion in breast lesions: the role of the epithelial-stroma barrier (2017)
Journal Article
Rakha, E. A., Miligy, I., Gorringe, K. L., Toss, M. S., Green, A. R., Fox, S. B., …Ellis, I. O. (2018). Invasion in breast lesions: the role of the epithelial-stroma barrier. Histopathology, 72(7), 1075-1083. https://doi.org/10.1111/his.13446

Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different... Read More about Invasion in breast lesions: the role of the epithelial-stroma barrier.

Diagnostic challenges in papillary lesions of the breast (2017)
Journal Article
Rakha, E. A., & Ellis, I. O. (2017). Diagnostic challenges in papillary lesions of the breast. Pathology, 50(1), (100-110). doi:10.1016/j.pathol.2017.10.005. ISSN 0031-3025

Papillary lesions of the breast comprise a heterogeneous group of diseases ranging from benign and atypical lesions to malignant tumours including non-invasive and invasive entities. Although diagnosis of papillary lesions featuring typical histologi... Read More about Diagnostic challenges in papillary lesions of the breast.

MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer (2017)
Journal Article
Craze, M. L., Cheung, H., Jewa, N., Coimbra, N. D., Soria, D., El-Ansari, R., …Green, A. R. (in press). MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer. British Journal of Cancer, https://doi.org/10.1038/bjc.2017.387

Background: Altered cellular metabolism is a hallmark of cancer and some are reliant on Glutamine for sustained proliferation and survival. We hypothesise that the Glutamine-Proline regulatory axis has a key role in Breast cancer (BC) in the highly p... Read More about MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer.

Evaluation of CDK12 protein expression as a potential novel biomarker for DNA damage response–targeted therapies in breast cancer (2017)
Journal Article
Naidoo, K., Wai, P. T., Maguire, S. L., Daley, F., Haider, S., Kriplani, D., …Natrajan, R. (2018). Evaluation of CDK12 protein expression as a potential novel biomarker for DNA damage response–targeted therapies in breast cancer. Molecular Cancer Therapeutics, 17(1), 306-315. https://doi.org/10.1158/1535-7163.mct-17-0760

Disruption of Cyclin-Dependent Kinase 12 (CDK12) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, CDK12 has also been proposed as an oncogene in breast cancer. We therefore aimed to assess t... Read More about Evaluation of CDK12 protein expression as a potential novel biomarker for DNA damage response–targeted therapies in breast cancer.

Reply to Rosen (2017)
Journal Article
Reis-Filho, J. S., Geyer, F. C., Weigelt, B., Rakha, E. A., Ellis, I. O., & Schnitt, S. J. (2017). Reply to Rosen. Modern Pathology, 30(10), 1505-1506. doi:10.1038/modpathol.2017.70

Altered glutamine metabolism in breast cancer: subtype dependencies and alternative adaptations (2017)
Journal Article
El Ansari, R., McIntyre, A., Craze, M. L., Ellis, I. O., Rakha, E. A., & Green, A. R. (in press). Altered glutamine metabolism in breast cancer: subtype dependencies and alternative adaptations. Histopathology, https://doi.org/10.1111/his.13334

Cancer cells must alter their metabolism in order to satisfy the demands of necessary energy and cellular building blocks. These metabolic alterations are mediated by many oncogenic changes that affect cellular signalling pathways, which result in su... Read More about Altered glutamine metabolism in breast cancer: subtype dependencies and alternative adaptations.

Current trials to reduce surgical intervention in ductal carcinoma in situ of the breast: critical review (2017)
Journal Article
Toss, M., Miligy, I., Thompson, A., Khout, H., Green, A., Ellis, I., & Rakha, E. (2017). Current trials to reduce surgical intervention in ductal carcinoma in situ of the breast: critical review. Breast, 35, 151-156. doi:10.1016/j.breast.2017.07.012

The high proportion of ductal carcinoma in situ (DCIS) presented in mammographic screening and the relatively low risk of progression to invasive disease have raised questions related to overtreatment. Following a review of current DCIS management pr... Read More about Current trials to reduce surgical intervention in ductal carcinoma in situ of the breast: critical review.

Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers (2017)
Journal Article
Klimov, S., Rida, P. C., Aleskandarany, M. A., Green, A. R., Ellis, I. O., Janssen, E. A., …Aneja, R. (2017). Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers. British Journal of Cancer, 117(6), 826-834. https://doi.org/10.1038/bjc.2017.224

Background: Although distant metastasis (DM) in breast cancer (BC) is the most lethal form of recurrence and the most common underlying cause of cancer related deaths, the outcome following the development of DM is related to the site of metastasis.... Read More about Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers.

FOXP1 expression correlates with better prognosis in invasive breast cancer including the ER-positive luminal subtype (2017)
Conference Proceeding
Joseph, C., Craze, M. L., Nolan, C., Diez-Rodriguez, M., Green, A. R., Rakha, E., …Mukherjee, A. (2017). FOXP1 expression correlates with better prognosis in invasive breast cancer including the ER-positive luminal subtype.

Background: Fork head box P1 (FOXP1) is a FOX family transcription factor influencing ERα;-regulated transcription by interaction with the ERα; related pioneer factor FOXA1. Altered FOXP1 expression is seen in breast and prostate cancers. This study... Read More about FOXP1 expression correlates with better prognosis in invasive breast cancer including the ER-positive luminal subtype.

Elevated expression of STK3 mRNA and protein is associated with poor outcome in invasive breast cancer (2017)
Conference Proceeding
Ojiegbe, S., Joseph, C., Provenzano, E., Caldas, C., Nolan, C., Green, A., …Mukherjee, A. (2017). Elevated expression of STK3 mRNA and protein is associated with poor outcome in invasive breast cancer.

Purpose of the study: The mammalian sterile 20-like kinase (MST2/STK3) and its close homologue MST1(STK4) are members of the germinal centre kinase group II (GCK II) family of mitogen-activated protein kinases (MAPK). High STK3 expression is known to... Read More about Elevated expression of STK3 mRNA and protein is associated with poor outcome in invasive breast cancer.

An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation (2017)
Journal Article
Candido Dos Reis, F. J., Wishart, G. C., Dicks, E. M., Greenberg, D., Rashbass, J., Schmidt, M. K., …Pharoah, P. D. (2017). An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation. Breast Cancer Research, 19(1), Article 58. https://doi.org/10.1186/s13058-017-0852-3

BACKGROUND: PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific morta... Read More about An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation.

Phenotypic characterization of breast cancer: the role of CDC42 (2017)
Journal Article
Chrysanthou, E., Gorringe, K. L., Joseph, C., Craze, M. L., Nolan, C. C., Diez-Rodriguez, M., …Mukherjee, A. (2017). Phenotypic characterization of breast cancer: the role of CDC42. Breast Cancer Research and Treatment, 164(2), https://doi.org/10.1007/s10549-017-4267-8

Purpose: The molecular landscape of breast cancer (BC), especially of the Luminal A subtype, remains to be fully delineated. Transcriptomic data shows that Luminal A tumours are enriched for aberrant expression of genes in the cell division control 4... Read More about Phenotypic characterization of breast cancer: the role of CDC42.

Chemokine (C-C motif) receptor 7 (CCR7) associates with the tumour immune microenvironment but not progression in invasive breast carcinoma (2017)
Journal Article
Sonbul, S. N., Gorringe, K. L., Aleskandarany, M. A., Mukherjee, A., Green, A. R., Ellis, I. O., & Rakha, E. A. (2017). Chemokine (C-C motif) receptor 7 (CCR7) associates with the tumour immune microenvironment but not progression in invasive breast carcinoma. Journal of Pathology: Clinical Research, 3(2), 105-114. https://doi.org/10.1002/cjp2.65

Some previous studies have reported that the chemokine (C-C motif) receptor 7 (CCR7) plays a role in breast cancer, is associated with lymph node metastasis and drives the site of distant metastasis. However, the impact of its expression on patient o... Read More about Chemokine (C-C motif) receptor 7 (CCR7) associates with the tumour immune microenvironment but not progression in invasive breast carcinoma.

Prognostic significance of tumour infiltrating B-Lymphocytes in breast ductal carcinoma in situ (2017)
Journal Article
Miligy, I., Mohan, P., Gaber, A., Aleskandarany, M. A., Nolan, C. C., Diez‐Rodriguez, M., …Rakha, E. A. (2017). Prognostic significance of tumour infiltrating B-Lymphocytes in breast ductal carcinoma in situ. Histopathology, 71(2), 258-268. https://doi.org/10.1111/his.13217

Aims: Tumour?infiltrating lymphocytes (TILs) are an important component of the immune response to cancer and have a prognostic value in breast cancer. Although several studies have investigated the role of T lymphocytes in breast cancer, the role of... Read More about Prognostic significance of tumour infiltrating B-Lymphocytes in breast ductal carcinoma in situ.

Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers (2017)
Journal Article
Green, A. R., Aleskandarany, M. A., Ali, R., Hodgson, E. G., Atabani, S., De Souza, K., …Madhusudan, S. (2017). Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers. Cancer Immunology Research, 5(4), 292-299. https://doi.org/10.1158/2326-6066.CIR-16-0195

© 2017 American Association for Cancer Research. Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand br... Read More about Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers.

Immunoprofile of metaplastic carcinomas of the breast (2017)
Journal Article
Rakha, E. A., Coimbra, N. D., Hodi, Z., Juneinah, E., Ellis, I. O., & Lee, A. H. (2017). Immunoprofile of metaplastic carcinomas of the breast. Histopathology, 70(6), (975-985). doi:10.1111/his.13159. ISSN 0309-0167

Aims Metaplastic breast carcinoma (MBC) is a rare type of breast cancer; its diagnosis in routine practice can be challenging, and may require immunohistochemical (IHC) characterization if no conventional invasive or in‐situ carcinoma is present. Pr... Read More about Immunoprofile of metaplastic carcinomas of the breast.

Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development (2017)
Journal Article
Metzler, V. M., de Brot, S., Robinson, R. S., Jeyapalan, J. N., Rakha, E., Walton, T., …Mongan, N. P. (2017). Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development. Placenta, 56, 79-85. https://doi.org/10.1016/j.placenta.2017.02.018

The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy,... Read More about Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development.

Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer (2016)
Journal Article
Rakha, E. A., Agarwal, D., Green, A. R., Ashankyty, I., Ellis, I. O., Ball, G., & Alaskandarany, M. A. (2017). Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer. Histopathology, 70(4), 622-631. doi:10.1111/his.13108

Aims Multigene assay is recommended currently for prognostic stratification of the clinically indeterminate group of breast cancer (BC) patients defined as lymph node (LN)?negative, oestrogen receptor (ER)?positive, HER2?negative (LN?/ER+/HER2?) t... Read More about Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer.

Molecular classification of breast cancer: what the pathologist needs to know (2016)
Journal Article
Rakha, E. A., & Green, A. R. (2017). Molecular classification of breast cancer: what the pathologist needs to know. Pathology, 49(2), 111-119. doi:10.1016/j.pathol.2016.10.012

Breast cancer is a heterogeneous disease featuring distinct histological, molecular and clinical phenotypes. Although traditional classification systems utilising clinicopathological and few molecular markers are well established and validated, they... Read More about Molecular classification of breast cancer: what the pathologist needs to know.

Diagnostic concordance of breast pathologists: lessons from the National Health Service Breast Screening Programme Pathology External Quality Assurance Scheme (2016)
Journal Article
Rakha, E. A., Ahmed, M. A., Aleskandarany, M. A., Hodi, Z., Lee, A. H. S., Pinder, S. E., & Ellis, I. O. (2017). Diagnostic concordance of breast pathologists: lessons from the National Health Service Breast Screening Programme Pathology External Quality Assurance Scheme. Histopathology, 70(4), 632-642. https://doi.org/10.1111/his.13117

DNA damage repair in breast cancer and its therapeutic implications (2016)
Journal Article
Ali, R., Rakha, E. A., Madhusudan, S., & Bryant, H. E. (2017). DNA damage repair in breast cancer and its therapeutic implications. Pathology, 49(2), 156-165. doi:10.1016/j.pathol.2016.11.002

The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in t... Read More about DNA damage repair in breast cancer and its therapeutic implications.

ADA3 regulates normal and tumor mammary epithelial cell proliferation through c-MYC (2016)
Journal Article
Griffin, N. I., Sharma, G., Zhao, X., Mirza, S., Srivastava, S., Dave, B. J., …Band, V. (2016). ADA3 regulates normal and tumor mammary epithelial cell proliferation through c-MYC. Breast Cancer Research, 18(1), 1-15. https://doi.org/10.1186/s13058-016-0770-9

Background: We have established the critical role of ADA3 as a coactivator of estrogen receptor (ER), as well as its role in cell cycle progression. Furthermore, we showed that ADA3 is predominantly nuclear in mammary epithelium, and in ER+, but is... Read More about ADA3 regulates normal and tumor mammary epithelial cell proliferation through c-MYC.

Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers (2016)
Journal Article
Arora, A., Parvathaneni, S., Aleskandarany, M. A., Agarwal, D., Ali, R., Abdel-Fatah, T., …Madhusudan, S. (2017). Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers. Molecular Cancer Therapeutics, 16(1), https://doi.org/10.1158/1535-7163.MCT-16-0290

RECQL1, a key member of the RecQ family of DNA helicases, is required for DNA replication and DNA repair. Two recent studies have shown that germline RECQL1 mutations are associated with increased breast cancer susceptibility. Whether altered RECQL1... Read More about Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers.

Breast conservation in ductal carcinoma in situ (DCIS): what defines optimal margins? (2016)
Journal Article
Toss, M. S., Pinder, S. E., Green, A. R., Thomas, J., Morgan, D. A., Robertson, J. F., …Rakha, E. A. (2017). Breast conservation in ductal carcinoma in situ (DCIS): what defines optimal margins?. Histopathology, 70(5), 681-692. https://doi.org/10.1111/his.13116

The introduction of mammographic screening has resulted in a rise in the detection rate of ductal carcinoma in situ (DCIS), currently accounting for one‐fifth of screen‐detected breast cancers. Although 60–70% of DCIS are treated with breast‐conservi... Read More about Breast conservation in ductal carcinoma in situ (DCIS): what defines optimal margins?.

Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival (2016)
Journal Article
Xuan, P., Storr, S. J., Zhang, Y., Rakha, E., Green, A. R., Ellis, I. O., & Martin, S. G. (in press). Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival. Apoptosis, https://doi.org/10.1007/s10495-016-1323-5

Impaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought... Read More about Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival.

Clinicopathological and molecular characteristics of Ku 70/80 expression in Nigerian breast cancer and its potential therapeutic implications (2016)
Journal Article
Agboola, A. O., Ebili, H. O., Iyawe, V. O., Banjo, A. A., Salami, B. A., Rakha, E. A., …Green, A. R. (2017). Clinicopathological and molecular characteristics of Ku 70/80 expression in Nigerian breast cancer and its potential therapeutic implications. Pathology - Research and Practice, 213(1), 27-33. https://doi.org/10.1016/j.prp.2016.10.005

Ku 70/80 is a regulator of the Non-Homologous End Joining (NHEJ) roles in clinicopathological features, and has prognostic significance in breast cancer (BC) in Caucasian populations. However, its significance in the Nigerian BC population, which is... Read More about Clinicopathological and molecular characteristics of Ku 70/80 expression in Nigerian breast cancer and its potential therapeutic implications.

Further evidence to support bimodality of oestrogen receptor expression in breast cancer (2016)
Journal Article
Muftah, A. A., Aleskandarany, M., Sonbul, S. N., Nolan, C. C., Diez Rodriguez, M., Caldas, C., …Rakha, E. A. (2017). Further evidence to support bimodality of oestrogen receptor expression in breast cancer. Histopathology, 70(3), 456-465. https://doi.org/10.1111/his.13089

Aims: Although oestrogen receptor (ER)‐negative breast cancers (BCs) do not respond to hormone therapy, the response of ER‐positive BCs is reported to be variable, which may suggest a dose‐dependent effect. The aim of this study was to assess the pat... Read More about Further evidence to support bimodality of oestrogen receptor expression in breast cancer.

Clinicopathological and prognostic significance of mitogen-activated protein kinases (MAPK) in breast cancers (2016)
Journal Article
Ahmad, D. A. J., Negm, O. H., Layth Alabdullah, M., Mirza, S., Hamed, M. R., Band, V., …Rakha, E. (2016). Clinicopathological and prognostic significance of mitogen-activated protein kinases (MAPK) in breast cancers. Breast Cancer Research and Treatment, 159(3), 457-467. https://doi.org/10.1007/s10549-016-3967-9

Background Mitogen-activated protein kinases (MAPKs) are signalling transduction molecules that have different functions and diverse behaviour in cancer. In breast cancer, MAPK is related to oestrogen receptor (ER) and HER2. Methods Protein express... Read More about Clinicopathological and prognostic significance of mitogen-activated protein kinases (MAPK) in breast cancers.

Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis (2016)
Journal Article
Aleskandarany, M. A., Abduljabbar, R., Ashankyty, I., Elmouna, A., Jerjees, D., Ali, S., …Rakha, E. A. (2016). Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis. Breast Cancer Research and Treatment, 159(2), 215-227. https://doi.org/10.1007/s10549-016-3934-5

Differential prognostic roles of Androgen Receptor (AR) have been proposed in breast cancer (BC) depending on tumour oestrogen receptor (ER) status. This study aimed to evaluate the prognostic and/or predictive significance of AR expression in invasi... Read More about Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis.

Papillary carcinoma of the breast: diagnostic agreement and management implications (2016)
Journal Article
Rakha, E. A., Ahmed, M. A., & Ellis, I. O. (2016). Papillary carcinoma of the breast: diagnostic agreement and management implications. Histopathology, 69(5), 862-870. doi:10.1111/his.13009

Aims Papillary carcinoma (PC), which is a rare type of breast cancer, comprises a heterogeneous group of tumours. The diagnostic categorization of PC as in?situ and invasive disease remains a matter of debate with respect to interpretation of its ov... Read More about Papillary carcinoma of the breast: diagnostic agreement and management implications.

Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein (2016)
Journal Article
Alshareeda, A., Negm, O. H., Aleskandarany, M. A., Green, A. R., Nolan, C., Tighe, P. J., …Rakha, E. (2016). Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein. Breast Cancer Research and Treatment, 159(1), 41-53. https://doi.org/10.1007/s10549-016-3915-8

Impaired DNA damage response (DDR) may play a fundamental role in the pathogenesis of breast cancer (BC). RAD51 is a key player in DNA double-strand break repair. In this study, we aimed to assess the biological and clinical significance of RAD51 exp... Read More about Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein.

Review of the national external quality assessment (EQA) scheme for breast pathology in the UK (2016)
Journal Article
Rakha, E. A., Bennett, R. L., Coleman, D., Pinder, S. E., & Ellis, I. O. (2017). Review of the national external quality assessment (EQA) scheme for breast pathology in the UK. Journal of Clinical Pathology, 70(1), 51-57. doi:10.1136/jclinpath-2016-203800

Background: The National Health Service Breast Screening Programme (NHSBSP; pathology) external quality assurance (EQA) scheme aims to provide a mechanism for examination and monitoring of concordance of pathology reporting within the UK. This study... Read More about Review of the national external quality assessment (EQA) scheme for breast pathology in the UK.

Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer (2016)
Journal Article
Aleskandarany, M. A., Green, A. R., Ashankyty, I., Elmouna, A., Diez-Rodriguez, M., Nolan, C. C., …Rakha, E. (in press). Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer. Breast Cancer Research and Treatment, 158(2), https://doi.org/10.1007/s10549-016-3893-x

In breast cancer (BC), the prognostic value of Ki67 expression is well-documented. Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The immunohist... Read More about Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer.

Overexpression of specific CD44 isoforms is associated with aggressive cell features in acquired endocrine resistance (2016)
Journal Article
Bellerby, R., Smith, C., Kyme, S., Gee, J., Günthert, U., Green, A., …Hiscox, S. (2016). Overexpression of specific CD44 isoforms is associated with aggressive cell features in acquired endocrine resistance. Frontiers in Oncology, 6, Article 145. https://doi.org/10.3389/fonc.2016.00145

While endocrine therapy is the mainstay of ER+ breast cancer, the clinical effectiveness of these agents is limited by the phenomenon of acquired resistance that is associated with disease relapse and poor prognosis. Our previous studies revealed tha... Read More about Overexpression of specific CD44 isoforms is associated with aggressive cell features in acquired endocrine resistance.

Expression of CDK7, cyclin H, and MAT1 is elevated in breast cancer and is prognostic in estrogen receptor-positive breast cancer (2016)
Journal Article
Patel, H., Abduljabbar, R., Lai, C., Periyasamy, M., Harrod, A., Gemma, C., …Ali, S. (2016). Expression of CDK7, cyclin H, and MAT1 is elevated in breast cancer and is prognostic in estrogen receptor-positive breast cancer. Clinical Cancer Research, 22(23), 5929-5938. https://doi.org/10.1158/1078-0432.ccr-15-1104

Purpose: CDK-activating kinase (CAK) is required for the regulation of the cell cycle and is a trimeric complex consisting of cyclin-dependent kinase 7 (CDK7), Cyclin H, and the accessory protein, MAT1. CDK7 also plays a critical role in regulating t... Read More about Expression of CDK7, cyclin H, and MAT1 is elevated in breast cancer and is prognostic in estrogen receptor-positive breast cancer.

Invasive lobular carcinoma mimicking papillary carcinoma: a report of three cases (2016)
Journal Article
Rakha, E. A., Abbas, A., & Sheeran, R. (2016). Invasive lobular carcinoma mimicking papillary carcinoma: a report of three cases. Pathobiology, 83(5), 221-227. doi:10.1159/000442884

Encapsulated and solid papillary carcinomas (EPCs and SPCs) are considered historically as a special form of ductal carcinoma in situ. Invasive lobular carcinoma (ILC) is characterised by a discohesive growth pattern. There are several variants of IL... Read More about Invasive lobular carcinoma mimicking papillary carcinoma: a report of three cases.

Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer (2016)
Journal Article
Green, A. R., Soria, D., Powe, D. G., Nolan, C. C., Aleskandarany, M. A., Szász, M., …Ellis, I. O. (2016). Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer. Breast Cancer Research and Treatment, 157(1), 65-75. https://doi.org/10.1007/s10549-016-3804-1

The Nottingham prognostic index plus (NPI+) is based on the assessment of biological class combined with established clinicopathologic prognostic variables providing improved patient outcome stratification for breast cancer superior to the traditiona... Read More about Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer.

Viewpoint: Availability of oestrogen receptor and HER2 status for the breast multidisciplinary meeting discussion; time to get it right (2016)
Journal Article
Francis, A., Bartlett, J., Rea, D., Pinder, S., Stein, R., Stobart, H., …Shaaban, A. (2016). Viewpoint: Availability of oestrogen receptor and HER2 status for the breast multidisciplinary meeting discussion; time to get it right. EJSO - European Journal of Surgical Oncology, 42(7), 994-998. https://doi.org/10.1016/j.ejso.2016.02.015

The efficacy and pivotal role of the multidisciplinary meeting (MDM) in informed decision making is well established. It aims to provide a forum in which clinical evidence combines with individual patient data to create a personalized treatment plan.... Read More about Viewpoint: Availability of oestrogen receptor and HER2 status for the breast multidisciplinary meeting discussion; time to get it right.

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours (2016)
Journal Article
Green, A. R., Aleskandarany, M. A., Agarwal, D., Elsheikh, S., Nolan, C. C., Diez-Rodriguez, M., …Rakha, E. A. (2016). MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours. British Journal of Cancer, 114(8), 917-928. https://doi.org/10.1038/bjc.2016.46

Background: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We... Read More about MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

The prognostic significance of STAT3 in invasive breast cancer: analysis of protein and mRNA expressions in large cohorts (2016)
Journal Article
Aleskandarany, M. A., Agarwal, D., Negm, O. H., Ball, G., Elmouna, A., Ashankyty, I., …Rakha, E. A. (2016). The prognostic significance of STAT3 in invasive breast cancer: analysis of protein and mRNA expressions in large cohorts. Breast Cancer Research and Treatment, 156(1), 9-20. https://doi.org/10.1007/s10549-016-3709-z

Signal transducer and activator of transcription (STAT) transcription factors family are involved in diverse cellular biological functions. Reports regarding the prognostic impact of STAT3 expression in breast cancer (BC) are variable whether being a... Read More about The prognostic significance of STAT3 in invasive breast cancer: analysis of protein and mRNA expressions in large cohorts.

RECQL4 helicase has oncogenic potential in sporadic breast cancers (2016)
Journal Article
Arora, A., Agarwal, D., Abdel-Fatah, T. M., Lu, H., Croteau, D. L., Moseley, P., …Madhusudan, S. (2016). RECQL4 helicase has oncogenic potential in sporadic breast cancers. Journal of Pathology, 238(4), 495-501. https://doi.org/10.1002/path.4681

RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund–Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer pr... Read More about RECQL4 helicase has oncogenic potential in sporadic breast cancers.

Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma (2016)
Journal Article
Laurinavicius, A., Plancoulaine, B., Rasmusson, A., Besusparis, J., Augulis, R., Meskauskas, R., …Ellis, I. O. (2016). Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma. Virchows Archiv, 468(4), 493-502. https://doi.org/10.1007/s00428-016-1907-z

Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and sign... Read More about Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.

Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile (2016)
Journal Article
Eberle, C. A., Piscuoglio, S., Rakha, E. A., Ng, C. K. Y., Geyer, F. C., Edelweiss, M., …Ellis, I. O. (2016). Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile. Histopathology, 68(7), 1030-1039. https://doi.org/10.1111/his.12897

Aims Infiltrating epitheliosis is a rare complex sclerosing lesion (CSL) of the breast, characterized by infiltrating ducts immersed in a scleroelastotic stroma and filled with cells having architectural and cytological patterns reminiscent of tho... Read More about Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile.

Human epidermal growth factor receptor 2 testing in invasive breast cancer: should histological grade, type and oestrogen receptor status influence the decision to repeat testing? (2016)
Journal Article
Rakha, E. A., Pigera, M., Shin, S. J., D'Alfonso, T., Ellis, I. O., & Lee, A. H. S. (2016). Human epidermal growth factor receptor 2 testing in invasive breast cancer: should histological grade, type and oestrogen receptor status influence the decision to repeat testing?. Histopathology, 69(1), 20-24. doi:10.1111/his.12900

Aims The recent American Society of Clinical Oncology/College of American Pathologists guidelines for human epidermal growth factor receptor 2 (HER2) testing in breast cancer recommend repeat testing based on tumour grade, tumour type, and hormone... Read More about Human epidermal growth factor receptor 2 testing in invasive breast cancer: should histological grade, type and oestrogen receptor status influence the decision to repeat testing?.

Clinical utility of reverse phase protein array for molecular classification of breast cancer (2015)
Journal Article
Negm, O. H., Muftah, A. A., Aleskandarany, M. A., Hamed, M. R., Ahmad, D. A., Nolan, C. C., …Green, A. R. (2016). Clinical utility of reverse phase protein array for molecular classification of breast cancer. Breast Cancer Research and Treatment, 155(1), 25-35. https://doi.org/10.1007/s10549-015-3654-2

Reverse Phase Protein Array (RPPA) represents a sensitive and high-throughput technique allowing simultaneous quantitation of protein expression levels in biological samples. This study aimed to confirm the ability of RPPA to classify archival formal... Read More about Clinical utility of reverse phase protein array for molecular classification of breast cancer.

An approach to the diagnosis of spindle cell lesions of the breast (2015)
Journal Article
Rakha, E. A., Aleskandarany, M. A., Lee, A. H. S., & Ellis, I. O. (2016). An approach to the diagnosis of spindle cell lesions of the breast. Histopathology, 68(1), 33-44. doi:10.1111/his.12865

Although most breast spindle cell lesions (BSCLs) are rare, they constitute a wide spectrum of diseases, ranging from reactive processes to aggressive malignant tumours. Despite their varied histogenesis and behaviour, some lesions show an overlap of... Read More about An approach to the diagnosis of spindle cell lesions of the breast.

Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers (2015)
Journal Article
Arora, A., Abdel-Fatah, T. M., Agarwal, D., Doherty, R., Croteau, D. L., Moseley, P. M., …Madhusudan, S. (2016). Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers. Carcinogenesis, 37(1), 63-71. https://doi.org/10.1093/carcin/bgv163

RECQL5 is a member of the RecQ family of DNA helicases and has key roles in homologous recombination, base excision repair, replication and transcription. The clinicopathological significance of RECQL5 expression in breast cancer is unknown. In this... Read More about Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers.

Nottingham Prognostic Index Plus: validation of a clinical decision making tool in breast cancer in an independent series (2015)
Journal Article
Green, A. R., Soria, D., Stephen, J., Powe, D. G., Nolan, C. C., Kunkler, I., …Ellis, I. O. (2016). Nottingham Prognostic Index Plus: validation of a clinical decision making tool in breast cancer in an independent series. Journal of Pathology: Clinical Research, 2, https://doi.org/10.1002/cjp2.32

The Nottingham Prognostic Index Plus (NPI+)is a clinical decision making tool in breast cancer (BC) that aims to provide improved patient outcome stratification superior to the traditional NPI. This study aimed to validate the NPI+ in an independent... Read More about Nottingham Prognostic Index Plus: validation of a clinical decision making tool in breast cancer in an independent series.

Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer (2015)
Journal Article
Alsubhi, N., Middleton, F., Abdel-Fatah, T. M., Stephens, P., Doherty, R., Arora, A., …Madhusudan, S. (2016). Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer. Molecular Oncology, 10(2), 213-223. https://doi.org/10.1016/j.molonc.2015.09.009

Radiation?induced DNA damage activates the DNA damage response (DDR). DDR up?regulation may predict radio?resistance and increase the risk of early local recurrence despite radiotherapy in early stage breast cancers. In 1755 early stage breast cancer... Read More about Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer.

Breast Neoplasms with Dermal Analogue Differentiation (Mammary Cylindroma): Report of 3 Cases and a Proposal for a New Terminology (2015)
Journal Article
Rakha, E. A., Lee, A. H., Sheeran, R., Abbosh, C., Hodi, Z., Merchant, W., …Shaaban, A. M. (2015). Breast Neoplasms with Dermal Analogue Differentiation (Mammary Cylindroma): Report of 3 Cases and a Proposal for a New Terminology. Pathobiology, 82(3-4), 172-178. https://doi.org/10.1159/000433600

Salivary gland-like and dermal analogue tumours of the breast are rare lesions that can be diagnostically challenging for pathologists. Data on the clinical behaviour and molecular characterisation of these mammary tumours are limited and their desig... Read More about Breast Neoplasms with Dermal Analogue Differentiation (Mammary Cylindroma): Report of 3 Cases and a Proposal for a New Terminology.

Construction of tissue microarrays from core needle biopsies: a systematic literature review (2015)
Journal Article
Albanghali, M., Green, A., Rakha, E., Aleskandarany, M., Nolan, C., Ellis, I., & Cheung, K. (2016). Construction of tissue microarrays from core needle biopsies: a systematic literature review. Histopathology, 68(3), 323-332. https://doi.org/10.1111/his.12802

In some clinical circumstances, core needle biopsy (CNB) may be the only source of material from cancer tissue for diagnostic use. The volume of tissue available in a CNB is low, and opportunities for research use can therefore be limited. The tissue... Read More about Construction of tissue microarrays from core needle biopsies: a systematic literature review.

Morphogenesis of the papillary lesions of the breast: phenotypic observation (2015)
Journal Article
Rakha, E. A. (2016). Morphogenesis of the papillary lesions of the breast: phenotypic observation. Journal of Clinical Pathology, 69(1), 64-69. doi:10.1136/jclinpath-2015-203191

Papillary lesions of the breast are a heterogeneous group of diseases characterised by the presence epithelial proliferation supported by fibrovascular stalks. Normal breast tissue does not show papillary morphology and the mechanisms underlying papi... Read More about Morphogenesis of the papillary lesions of the breast: phenotypic observation.

Pleomorphic adenoma-like tumour of the breast (2015)
Journal Article
Rakha, E. A., Aleskandarany, M. A., Samaka, R. M., Hodi, Z., Lee, A. H., & Ellis, I. O. (2016). Pleomorphic adenoma-like tumour of the breast. Histopathology, 68(3), 405-410. doi:10.1111/his.12757

The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer (2015)
Journal Article
Magnani, L., Patten, D. K., Nguyen, V. T. M., Hong, S., Steel, J. H., Patel, N., …Coombes, C. R. (2015). The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer. Oncotarget, 6(26), 21878-21891. https://doi.org/10.18632/oncotarget.4243

Over 30% of ER? breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ER? binding. Here we demonstrate t... Read More about The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer.

A case-controlled study of the oncologic safety of fat grafting (2015)
Journal Article
Gale, K. L., Rakha, E. A., Ball, G., Tan, V. K., McCulley, S. J., & Macmillan, R. D. (2015). A case-controlled study of the oncologic safety of fat grafting. Plastic and Reconstructive Surgery, 135(5), 1263-1275. doi:10.1097/prs.0000000000001151

DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers (2015)
Journal Article
Abdel-Fatah, T. M., Arora, A., Moseley, P. M., Perry, C., Rakha, E. A., Green, A. R., …Madhusudan, S. (2015). DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers. Oncotarget, 6(26), 21964-21978. https://doi.org/10.18632/oncotarget.4157

Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol β,... Read More about DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers.

KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer (2015)
Journal Article
Alshareeda, A., Negm, O., Green, A., Nolan, C., Tighe, P., Albarakati, N., …Rakha, E. (2015). KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer. British Journal of Cancer, 112(12), 1929–1937. https://doi.org/10.1038/bjc.2015.165

Background: It is recognised that modulations of the nuclear import of macromolecules have a role in changing cellular phenotypes and carcinogenesis. We and others have noticed that aberrant subcellular localisation of DNA damage response (DDR) prote... Read More about KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer.

Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification (2015)
Journal Article
Aleskandarany, M. A., Soria, D., Green, A. R., Nolan, C., Diez-Rodriguez, M., Ellis, I. O., & Rakha, E. A. (2015). Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification. Breast Cancer Research and Treatment, 151(2), 325-333. https://doi.org/10.1007/s10549-015-3406-3

Accurate distant metastasis (DM) prediction is critical for risk stratification and effective treatment decisions in breast cancer (BC). Many prognostic markers/models based on tissue marker studies are continually emerging using conventional statist... Read More about Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification.

Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents (2015)
Journal Article
Ong, C. C., Gierke, S., Pitt, C., Sagolla, M., Cheng, C. K., Zhou, W., …Hoeflich, K. P. (2015). Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents. Breast Cancer Research, 17(1), Article 59. https://doi.org/10.1186/s13058-015-0564-5

Introduction Breast cancer, the most common cause of cancer-related deaths worldwide among women, is a molecularly and clinically heterogeneous disease. Extensive genetic and epigenetic profiling of breast tumors has recently revealed novel puta... Read More about Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents.

FKBPL: a marker of good prognosis in breast cancer (2015)
Journal Article
Nelson, L., McKeen, H. D., Ellis, I., Rakha, E., Marshall, A., Mulrane, L., …Robson, T. (2015). FKBPL: a marker of good prognosis in breast cancer. Oncotarget, 6(14), 12209-12223. https://doi.org/10.18632/oncotarget.3528

FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL’s prognostic ability in primary breast... Read More about FKBPL: a marker of good prognosis in breast cancer.

Inflammatory breast cancer: time to standardise diagnosis assessment and management and for the joining of forces to facilitate effective research (2015)
Journal Article
Rea, D., Francis, A., Hanby, A., Speirs, V., Rakha, E., Shaaban, A., …on behalf of the UK Inflammatory Breast Cancer Working group. (2015). Inflammatory breast cancer: time to standardise diagnosis assessment and management and for the joining of forces to facilitate effective research. British Journal of Cancer, 112(9), 1613-1615. https://doi.org/10.1038/bjc.2015.115

Are acinic cell carcinomas of the breast and salivary glands distinct diseases? (2015)
Journal Article
Piscuoglio, S., Hodi, Z., Katabi, N., Guerini-Rocco, E., Macedo, G. S., Ng, C. K., …Reis-Filho, J. S. (2015). Are acinic cell carcinomas of the breast and salivary glands distinct diseases?. Histopathology, 67(4), 529-537. https://doi.org/10.1111/his.12673

Aims: Acinic cell carcinomas (AcCC) of the breast have been reported to constitute the breast counterpart of salivary gland AcCCs, based on the similarities of their histological and immunohistochemical features. Breast AcCC is a vanishingly rare for... Read More about Are acinic cell carcinomas of the breast and salivary glands distinct diseases?.

Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer (2015)
Journal Article
Abduljabbar, R., Negm, O. H., Lai, C., Jerjees, D. A., Al-Kaabi, M., Hamed, M. R., …Ellis, I. O. (2015). Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer. Breast Cancer Research and Treatment, 150(2), 335-346. https://doi.org/10.1007/s10549-015-3335-1

The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily of transcription factors, which exerts anti-proliferative and anti-apoptotic activities. The GR is expressed in a large proportion of breast cancer (BC) although levels... Read More about Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer.

Macroscopic handling and reporting of breast cancer specimens pre- and post-neoadjuvant chemotherapy treatment: review of pathological issues and suggested approaches (2015)
Journal Article
Pinder, S. E., Rakha, E. A., Purdie, C. A., Bartlett, J. M. S., Francis, A., Stein, R. C., …the Translational Subgroup of the NCRI Breast Clinical Studies Group. (2015). Macroscopic handling and reporting of breast cancer specimens pre- and post-neoadjuvant chemotherapy treatment: review of pathological issues and suggested approaches. Histopathology, 67(3), 279-293. https://doi.org/10.1111/his.12649

Neoadjuvant chemotherapy (NACT) is used increasingly in the treatment of invasive breast cancer and presents challenges for the pathologist in the handling and interpretation of tissues. Potential issues include pathological identification and locali... Read More about Macroscopic handling and reporting of breast cancer specimens pre- and post-neoadjuvant chemotherapy treatment: review of pathological issues and suggested approaches.

The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways (2015)
Journal Article
Jerjees, D. A., Negm, O. H., Alabdullah, M. L., Mirza, S., Alkaabi, M., Hameed, M. R., …Rakha, E. A. (2015). The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways. Breast Cancer Research and Treatment, 150(1), 91-103. https://doi.org/10.1007/s10549-015-3308-4

The mammalian target of rapamycin complex 1 (mTORC1) is a downstream of the PI3K/Akt pathway which affects cancer development. mTORC1 has many downstream signalling effectors that can enhance different cellular responses. This study aims to investiga... Read More about The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways.

DNA damage response markers are differentially expressed in BRCA-mutated breast cancers (2015)
Journal Article
Aleskandarany, M., Caracappa, D., Nolan, C. C., Macmillan, R. D., Ellis, I. O., Rakha, E. A., & Green, A. R. (2015). DNA damage response markers are differentially expressed in BRCA-mutated breast cancers. Breast Cancer Research and Treatment, 150(1), 81-90. https://doi.org/10.1007/s10549-015-3306-6

Cells have stringent DNA repair pathways that are specific for each different set of DNA lesions which is accomplished through the integration of complex array of proteins. However, BRCA-mutated breast cancer (BC) has defective DNA repair mechanisms.... Read More about DNA damage response markers are differentially expressed in BRCA-mutated breast cancers.

Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response (2015)
Journal Article
Al-kaabi, M., Alshareeda, A., Jerjees, D., Muftah, A., Green, A., Alsubhi, N., …Rakha, E. (2015). Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response. British Journal of Cancer, 112(5), 901-911. https://doi.org/10.1038/bjc.2014.576

Background: Checkpoint kinase1 (CHK1), which is a key component of DNA-damage-activated checkpoint signalling response, may have a role in breast cancer (BC) pathogenesis and influence response to chemotherapy. This study investigated the clinicop... Read More about Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response.

Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer (2015)
Journal Article
Arora, A., Abdel-Fatah, T., Agarwal, D., Doherty, R., Moseley, P. M., Aleskandarany, M. A., …Madhusudan, S. (2015). Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer. Molecular Cancer Therapeutics, 14(4), https://doi.org/10.1158/1535-7163.MCT-14-0939

Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition... Read More about Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer.

Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer (2014)
Journal Article
Davis, J., Martin, S. G., Patel, P. M., Green, A. R., Rakha, E. A., Ellis, I. O., & Storr, S. J. (2014). Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer. BMC Cancer, 14(1), https://doi.org/10.1186/1471-2407-14-995

Background The calpains are intracellular cysteine proteases that function in a variety of important cellular functions, including signalling, motility, apoptosis and survival. In breast cancer high calpain-1 and calpain-2 expression has been asso... Read More about Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer.

High-grade encapsulated papillary carcinoma of the breast: an under-recognized entity (2014)
Journal Article
Rakha, E. A., Varga, Z., Elsheik, S., & Ellis, I. O. (2015). High-grade encapsulated papillary carcinoma of the breast: an under-recognized entity. Histopathology, 66(5), 740-746. doi:10.1111/his.12591

Aims Encapsulated papillary carcinoma (EPC) is a recognized special type of breast carcinoma. Despite compelling evidence indicating its invasive nature, although not of a conventional form, the current consensus is to manage EPC as an in?situ disea... Read More about High-grade encapsulated papillary carcinoma of the breast: an under-recognized entity.

Biological and clinical significance of PARP1 protein expression in breast cancer (2014)
Journal Article
Green, A. R., Caracappa, D., Benhasouna, A. A., Alshareeda, A., Nolan, C. C., Macmillan, R. D., …Rakha, E. A. (2015). Biological and clinical significance of PARP1 protein expression in breast cancer. Breast Cancer Research and Treatment, 149(2), 353-362. https://doi.org/10.1007/s10549-014-3230-1

Poly(ADP-ribose) polymerase-1 (PARP1) is a key facilitator of DNA repair. PARP inhibitors have gained recent attention as promising therapeutic agents for the treatment of solid tumours including breast cancer (BC). However, the biological and clinic... Read More about Biological and clinical significance of PARP1 protein expression in breast cancer.

Updated UK recommendations for HER2 assessment in breast cancer (2014)
Journal Article
Rakha, E. A., Pinder, S. E., Bartlett, J. M., Ibrahim, M., Starczynski, J., Carder, P. J., …Ellis, I. O. (2015). Updated UK recommendations for HER2 assessment in breast cancer. Journal of Clinical Pathology, 68(2), 93-99. https://doi.org/10.1136/jclinpath-2014-202571

Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 15% of early invasive breast cancers, and is an important predictive and prognostic marker. The substantial benefits achieved with anti-HER2 targeted therapies... Read More about Updated UK recommendations for HER2 assessment in breast cancer.

Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer (2014)
Journal Article
Wishart, G. C., Rakha, E., Green, A., Ellis, I., Ali, H. R., Provenzano, E., …Pharoah, P. D. (2014). Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer. BMC Cancer, 14(1), Article 908. https://doi.org/10.1186/1471-2407-14-908

Background PREDICT (http://www.predict.nhs.uk) is a prognostication and treatment benefit tool for early breast cancer (EBC). The aim of this study was to incorporate the prognostic effect of KI67 status in a new version (v3), and compare performa... Read More about Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer.

Prognostic factors in metaplastic carcinoma of the breast: a multi-institutional study (2014)
Journal Article
Rakha, E. A., Tan, P. H., Varga, Z., Tse, G. M., Shaaban, A. M., Climent, F., …Chan, T. (2015). Prognostic factors in metaplastic carcinoma of the breast: a multi-institutional study. British Journal of Cancer, 112(2), 283-289. https://doi.org/10.1038/bjc.2014.592

Background: Metaplastic breast carcinoma (MBC) is a rare type of breast cancer that has basal-like characteristics and is perceived to have poorer prognosis when compared with conventional no specific type/ductal carcinomas (ductal/NST). However, cu... Read More about Prognostic factors in metaplastic carcinoma of the breast: a multi-institutional study.

Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts (2014)
Journal Article
Abdel-Fatah, T. M., Arora, A., Alsubhi, N., Agarwal, D., Moseley, P. M., Perry, C., …Madhusudan, S. (2014). Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts. Neoplasia, 16(11), 982-991. https://doi.org/10.1016/j.neo.2014.09.009

ATM-Chk2 network is critical for genomic stability, and its deregulation may influence breast cancer pathogenesis. We investigated ATM and Chk2 protein levels in two cohorts [cohort 1 (n = 1650) and cohort 2 (n = 252)]. ATM and Chk2 mRNA expression w... Read More about Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts.

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer (2014)
Journal Article
Abdel-Fatah, T. M., Middleton, F. K., Arora, A., Agarwal, D., Chen, T., Moseley, P. M., …Madhusudan, S. (2015). Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer. Molecular Oncology, 9(3), 569-585. https://doi.org/10.1016/j.molonc.2014.10.013

ATR?CHEK1 signalling is critical for genomic stability. ATR?CHEK1 signalling may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. We investigated ATR, CHEK1 and phosphorylated CHEK1 Ser345 protein (pCHEK1)... Read More about Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer.

Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy (2014)
Journal Article
Zhang, Y., Storr, S. J., Johnson, K., Green, A. R., Rakha, E. A., Ellis, I. O., …Martin, S. G. (2014). Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy. Oncotarget, 5(24), https://doi.org/10.18632/oncotarget.2683

Metformin is under evaluation as a potential anticancer agent. Expression of total and phospho(Thr172)-adenosine monophosphate-activated kinase-α (AMPKα and pAMPKα(Thr172) respectively), a main metformin target, was examined in radiotherapy treated b... Read More about Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy.

Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells (2014)
Journal Article
Filipović, A., Lombardo, Y., Fronato, M., Abrahams, J., Aboagye, E., Nguyen, Q., …Coombes, R. C. (2014). Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells. Breast Cancer Research and Treatment, 148(2), 455-462. https://doi.org/10.1007/s10549-014-3119-z

The goal of targeted cancer therapies is to specifically block oncogenic signalling, thus maximising efficacy, while reducing side-effects to patients. The gamma-secretase (GS) complex is an attractive therapeutic target in haematological malignancie... Read More about Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells.

Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy (2014)
Journal Article
Albarakati, N., Abdel-Fatah, T. M., Doherty, R., Russell, R., Agarwal, D., Moseley, P., …Madhusudan, S. (2015). Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy. Molecular Oncology, 9(1), 204-217. https://doi.org/10.1016/j.molonc.2014.08.001

BRCA1, a key factor in homologous recombination (HR) repair may also regulate base excision repair (BER). Targeting BRCA1?BER deficient cells by blockade of ATM and DNA?PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1... Read More about Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy.

ERK1/2 is related to oestrogen receptor and predicts outcome in hormone-treated breast cancer (2014)
Journal Article
Jerjees, D. A., Alabdullah, M., Alkaabi, M., Abduljabbar, R., Muftah, A., Nolan, C., …Rakha, E. A. (2014). ERK1/2 is related to oestrogen receptor and predicts outcome in hormone-treated breast cancer. Breast Cancer Research and Treatment, 147(1), 25-37. https://doi.org/10.1007/s10549-014-3066-8

The extracellular-regulated kinase (ERK) 1/2 is one of the members of the mitogen-activated protein kinases (MAPKs). MAPKs are transduction proteins that play a role in controlling diverse cellular functions including proliferation and survival. In b... Read More about ERK1/2 is related to oestrogen receptor and predicts outcome in hormone-treated breast cancer.

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers (2014)
Journal Article
Abdel-Fatah, T., Arora, A., Agarwal, D., Moseley, P., Perry, C., Thompson, N., …Madhusudan, S. (2014). Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers. Breast Cancer Research and Treatment, 146(2), 309-320. https://doi.org/10.1007/s10549-014-3035-2

DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end-joining pathway required fo... Read More about Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers.

Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study (2014)
Journal Article
Aleskandarany, M. A., Negm, O. H., Green, A. R., Ahmed, M. A. H., Nolan, C. C., Tighe, P. J., …Rakha, E. A. (2014). Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study. Breast Cancer Research and Treatment, 145(2), 339-348. https://doi.org/10.1007/s10549-014-2927-5

Epithelial mesenchymal transition (EMT), as defined by loss of epithelial characteristics and gain of a mesenchymal phenotype, has been reported in vivo although the occurrence of events remains unclear. This study aims at exploration of EMT portrait... Read More about Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study.

Prognostic and biological significance of proliferation and HER2 expression in the luminal class of breast cancer (2014)
Journal Article
Jerjees, D. A., Alabdullah, M., Green, A. R., Alshareeda, A., Macmillan, R. D., Ellis, I. O., & Rakha, E. A. (2014). Prognostic and biological significance of proliferation and HER2 expression in the luminal class of breast cancer. Breast Cancer Research and Treatment, 145(2), 317-330. doi:10.1007/s10549-014-2941-7

The definition of Luminal-B subclass of breast cancer (BC) varies in literature. In this study, we have compared the proliferation status; assessed using KI67 labeling index (KI67-LI), and HER2-expression in estrogen receptor positive (ER+) BC to ass... Read More about Prognostic and biological significance of proliferation and HER2 expression in the luminal class of breast cancer.

HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer (2014)
Journal Article
Green, A. R., Barros, F. F., Abdel-Fatah, T. M., Moseley, P., Nolan, C. C., Durham, A. C., …Ellis, I. O. (2014). HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer. Breast Cancer Research and Treatment, 145(1), 33-44. https://doi.org/10.1007/s10549-014-2925-7

Human epidermal growth factor receptor 2 (HER2) plays an important role in breast cancer progression and provides predictive information for response to targeted therapy including trastuzumab although this is limited. Downstream pathways, such as PI3... Read More about HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer.

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer (2014)
Journal Article
Rakha, E., Soria, D., Green, A. R., Lemetre, C., Powe, D. G., Nolan, C. C., …Ellis, I. O. (2014). Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer. British Journal of Cancer, 110(7), https://doi.org/10.1038/bjc.2014.120

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. I... Read More about Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

SUMOylation proteins in breast cancer (2014)
Journal Article
Alshareeda, A. T., Negm, O. H., Green, A. R., Nolan, C., Tighe, P., Albarakati, N., …Rakha, E. A. (2014). SUMOylation proteins in breast cancer. Breast Cancer Research and Treatment, 144(3), 519-530. https://doi.org/10.1007/s10549-014-2897-7

Small Ubiquitin-like Modifier proteins (or SUMO) modify the function of protein substrates involved in various cellular processes including DNA damage response (DDR). It is becoming apparent that dysregulated SUMO contribute to carcinogenesis by affe... Read More about SUMOylation proteins in breast cancer.

Characterisation of HER heterodimers in breast cancer using in situ proximity ligation assay (2014)
Journal Article
Barros, F. F., Abdel-Fatah, T. M., Moseley, P., Nolan, C. C., Durham, A. C., Rakha, E. A., …Green, A. R. (2014). Characterisation of HER heterodimers in breast cancer using in situ proximity ligation assay. Breast Cancer Research and Treatment, 144(2), 273-285. https://doi.org/10.1007/s10549-014-2871-4

HER2 plays an important role in breast cancer progression and provides predictive and prognostic information. HER2 receptor family members function through dimerisation, which can lead to impact on cell function, growth and differentiation; however,... Read More about Characterisation of HER heterodimers in breast cancer using in situ proximity ligation assay.

PIAS? expression in relation to clinicopathological, tumour factors and survival in indigenous black breast cancer women (2013)
Journal Article
Agboola, A., Musa, A., Banjo, A., Ayoade, B., Deji-Agboola, M., Nolan, C., …Green, A. (2014). PIASγ expression in relation to clinicopathological, tumour factors and survival in indigenous black breast cancer women. Journal of Clinical Pathology, 67(4), 301-306. https://doi.org/10.1136/jclinpath-2013-201658

Aim: Indigenous black women with breast cancer (BC) show a high frequency of triple negative breast cancer (TNBC) comprising ER-, PR- and HER2- phenotypes and BRCA1 deficiency together with a high mortality rate, prompting speculation that risk facto... Read More about PIAS? expression in relation to clinicopathological, tumour factors and survival in indigenous black breast cancer women.

C-Met in invasive breast cancer: is there a relationship with the basal-like subtype? (2013)
Journal Article
Ho-Yen, C. M., Green, A. R., Brentnall, A. R., Rakha, E. A., Ellis, I. O., Kermorgant, S., & Jones, J. L. (2014). C-Met in invasive breast cancer: is there a relationship with the basal-like subtype?. Cancer, 120(2), 163-171. doi:10.1002/cncr.28386

BACKGROUND Basal?like (BL) breast cancer is an aggressive form of breast cancer with limited treatment options. Recent work has identified BL breast cancer as a biologically distinct form of triple?negative breast cancer, with a worse outlook. The... Read More about C-Met in invasive breast cancer: is there a relationship with the basal-like subtype?.

Clinicopathological and molecular significance of Sumolyation marker (ubiquitin conjugating enzyme 9 (UBC9)) expression in breast cancer of black women (2013)
Journal Article
Agboola, A. J., Musa, A., Ayoade, B., Banjo, A., Anunobi, C., Deji-Agboola, A., …Green, A. (2014). Clinicopathological and molecular significance of Sumolyation marker (ubiquitin conjugating enzyme 9 (UBC9)) expression in breast cancer of black women. Pathology - Research and Practice, 210(1), 10-17. https://doi.org/10.1016/j.prp.2013.09.011

The majority of breast cancers (BC) in Nigerian women are triple negative and show breast cancer-associated gene 1 (BRCA1) deficiency as well as the basal like phenotype, with a high mortality rate. In contrast to the well-defined predictive factors... Read More about Clinicopathological and molecular significance of Sumolyation marker (ubiquitin conjugating enzyme 9 (UBC9)) expression in breast cancer of black women.

A methodology to identify consensus classes from clustering algorithms applied to immunohistochemical data from breast cancer patients (2010)
Journal Article
Soria, D., Garibaldi, J. M., Ambrogi, F., Green, A. R., Powe, D., Rakha, E., …Ellis, I. O. (2010). A methodology to identify consensus classes from clustering algorithms applied to immunohistochemical data from breast cancer patients. Computers in Biology and Medicine, 40(3), https://doi.org/10.1016/j.compbiomed.2010.01.003

Single clustering methods have often been used to elucidate clusters in high dimensional medical data, even though reliance on a single algorithm is known to be problematic. In this paper, we present a methodology to determine a set of ‘core classes’... Read More about A methodology to identify consensus classes from clustering algorithms applied to immunohistochemical data from breast cancer patients.