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
Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Sagamu, Nigeria.
Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Sagamu, Nigeria.
Pathol Res Pract. 2017 Jan;213(1):27-33. doi: 10.1016/j.prp.2016.10.005. Epub 2016 Oct 25.
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.
Ku70/80是一种在临床病理特征中调节非同源末端连接（NHEJ）作用的因子，在白种人群的乳腺癌（BC）中具有预后意义。然而，其在以三阴性和基底细胞表型、p53突变率和BRCA1缺陷发生率较高为特征的尼日利亚BC人群中的意义仍有待研究。我们假设Ku70/80表达在尼日利亚BC中呈不良表达，此外，它可能对黑人BC的治疗具有指导意义。本研究调查了Ku70/80表达在尼日利亚人群BC队列中的生物学、临床病理及预后意义。使用组织芯片和免疫组化方法，在188份特征明确的福尔马林固定、石蜡包埋（FFPE）的BC样本中检测Ku70/80表达。将Ku70/80表达与患者的临床病理、分子及预后特征进行关联分析。113例（60.1%）肿瘤中检测到Ku70/80表达，其与转移性疾病、三阴性和基底细胞表型、BRCA1下调因子（MTA-1和ID4）、p-钙黏蛋白、PI3KCA和p53表达呈正相关。它与BRCA1、BRCA2、BARD1和p27呈负相关。在多变量分析中，Ku70/80可预测乳腺癌特异性生存，但不能预测无病生存期。本研究表明，Ku70/80表达与三阴性及DNA修复同源重组途径下调相关。因此，开发靶向KU70/80的新型药物可能改善黑人BC患者的治疗结局。
