title: Clinicopathological and molecular characteristics of Ku 70/80 expression in Nigerian breast cancer and its potential therapeutic implications.
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.
authors.affiliation: Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Sagamu, Nigeria. Electronic address: Johndeji2001@yahoo.co.uk.
authors.forename: Ayodeji O J
authors.initials: AO
authors.lastname: Agboola
authors.affiliation: Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: Henry O
authors.initials: HO
authors.lastname: Ebili
authors.affiliation: Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: Victoria O
authors.initials: VO
authors.lastname: Iyawe
authors.affiliation: Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: Adekunbiola A F
authors.initials: AA
authors.lastname: Banjo
authors.affiliation: Department of Surgery, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: Babatunde A
authors.initials: BA
authors.lastname: Salami
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom.
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom.
authors.forename: Chrstopher C
authors.initials: CC
authors.lastname: Nolan
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom.
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D044383:Black People; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000072200:Ku Autoantigen / Q000378:metabolism*; D008875:Middle Aged; D009549:Nigeria; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D000072200:Ku Autoantigen
keywords: Biological; Clinicopathological; Ku 70/80; Nigerian breast cancer; Prognosis