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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.

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.

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.

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.