Clinicopathological and molecular characteristics of Ku 70/80 expression in Nigerian breast cancer and its potential therapeutic implications

Agboola, Ayodeji O.J.; Ebili, Henry O.; Iyawe, Victoria O.; Banjo, Adekunbiola A.F.; Salami, Babatunde A.; Rakha, Emad A.; Nolan, Chrstopher C.; Ellis, Ian O.; Green, Andrew R.

Abstract

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 characterized by a higher rate of the triple-negative and basal phenotype, p53 mutation rate and BRCA1 deficiency, still needs to be investigated. We hypothesize that Ku70/80 expression shows adverse expression in Nigerian BC and, furthermore, that it is likely to have a therapeutic implication for Black BC management.
This study investigated the biological, clinicopathological and prognostic significance of Ku 70/80 expression in a BC cohort from a Nigerian population. Ku 70/80 expression was determined in 188 well-characterized formalin-fixed, paraffin-embedded (FFPE) BC samples using tissue microarray and immunohistochemistry. Ku 70/80 expression was correlated with clinicopathological, molecular and prognostic characteristics of patients.
Ku 70/80 was expressed in 113 (60.1%) tumors, and was positively associated with metastatic disease, triple-negative and basal phenotype, BRCA1 down regulators (MTA-1 and ID4), p-cadherin, PI3KCA and p53 expression. It inversely correlated with BRCA1, BRCA2, BARD1 and p27. Ku 70/80 was predictive of breast cancer-specific survival in multivariate analysis, but not of disease-free interval.
This study demonstrated that Ku 70/80 expression is associated with triple negativity and down-regulation of the homologous recombination pathway of DNA repair. Therefore, the development of novel drugs to target KU70/80 may improve the patients’ outcome in the treatment of Black BC.

Citation

Agboola, A. O., Ebili, H. O., Iyawe, V. O., Banjo, A. A., Salami, B. A., Rakha, E. A., Nolan, C. C., Ellis, I. O., & 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

• Journal Article Type: Article
• Acceptance Date: Oct 17, 2016
• Online Publication Date: Oct 25, 2016
• Publication Date: Jan 30, 2017
• Deposit Date: Oct 15, 2018
• Publicly Available Date: Oct 16, 2018
• Journal: Pathology - Research and Practice
• Print ISSN: 0344-0338
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 213
• Issue: 1
• Pages: 27-33
• DOI: https://doi.org/10.1016/j.prp.2016.10.005
• Keywords: Pathology and Forensic Medicine; Cell Biology
• Public URL: https://nottingham-repository.worktribe.com/output/1166716
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0344033816305465
• Contract Date: Oct 16, 2018