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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.

The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion (2023)
Journal Article
Aljohani, A., Alsaeed, S., Toss, M., Raafat, S., GREEN, A., & Rakha, E. (2023). The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion. American Journal of Cancer Research, 13(11), 5334–5351

Lymphovascular invasion (LVI) is a common phenomenon in breast cancer (BC), and it is correlated to poor outcome. However, the biomarkers that influence the development of LVI remain to be defined. Through rigorous bioinformatics analyses, high mobil... Read More about The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion.

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.

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.

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.

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.