Differential expression of cellular senescence markers in the assessment of breast cancer development

Abstract

Breast cancer is a heterogeneous disease displaying different histopathological characteristics, biomarker expression profiles and clinical behaviour. Senescence-associated biomarkers exhibit distinctive molecular changes at different stages of cancer development which can be used for molecular characterisation of breast cancer. The research programme described in this thesis aims to characterize the expression patterns of the senescence markers P14, P16, P21, P53, DCR2 and DEC1 during cancer progression in a large cohort of breast cancer patients. A retrospective study of 1080 patients with invasive ductal carcinoma, of no special type, spanning over an 11 year period, was investigated. Immunohistochemical staining was performed on tissue microarrays that include normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma from each patient. Pearson chi-square was undertaken to determine the associations, Kaplan-Meier log rank test to study the survival analyses and Cox proportional hazard regression test to identify independent predictors of patient prognosis. Invasive ductal carcinomas demonstrated greater expression of P14, P16, p53 and DCR2, but lower expression of P21 and DEC1 when compared to non-malignant tissues. There was a significant correlation between normal, benign, premalignant and malignant tissues with P14, P21, P16, P53, DCR2 and DEC1 expression (p

Date of Award	2016
Original language	English