41. Differences in cell cycle and apoptotic biomarker expression between molecular subtypes of invasive ductal breast carcinoma

Abstract

Breast cancer is a heterogeneous disease that can be stratified into at least five subtypes by gene expression analysis or immunohis-tochemical biomarkers. Our aim was to identify differences in the expression of candidate cell cycle and apoptotic biomarkers between these subtypes. We assembled a cohort of 292 patients with early invasive ductal carcinoma and comprehensive clinical follow-up. Using immunohistochemical (ER, PR, CK5/6, EGFR and Ki67) or fluorescent in situ hybridisation (HER2), surrogate signatures for the intrinsic molecular subtypes were defined as follows: Luminal A – ER positive and/or PR positive, HER2 FISH negative, Ki67 low; Luminal B – ER positive and/or PR positive, HER2 FISH positive and/or Ki67 high; HER2 subtype – ER and PR negative, HER2 FISH positive; Basal-like subtype – ER negative, PR negative, HER2 FISH negative, CK 5/6 positive and/or EGFR positive; 5 marker negative – negative for ER, PR, HER2, CK5/6 and EGFR. These signatures were then used to compare the expression of hormone receptors (ER, PR), cell cycle proteins (cyclin D1, cyclin E1, p21WAF1/Cip1, p27Kip) as well as markers of apoptosis (cleaved PARP and TP53) between the molecular subtypes. Luminal A and B subgroups were characterised by a high expression of cyclin D1 (all p The basal-like tumours were characterised by a high cyclin E1 expression (all p These data identify important differences in the expression of a number of cell cycle proteins and TP53 between biomarker-defined breast cancer subtypes. These data may direct further research evaluating the biological aberrations underpinning individual subtypes, their resistance to specific therapies and potential vulnerabilities to new therapeutic approaches.