CCND1 amplification and cyclin D1 expression in breast cancer and their relation with proteomic subgroups and patient outcome

Abstract

Despite strong evidence regarding the role of CCND1 amplification and protein overexpression in breast carcinoma, the associations between CCND1 amplification/cyclin D1 overexpression and clinicopathological variables and clinical outcome remain controversial. (1) to correlate cyclin D1 expression with gene amplification; (2) to analyse the correlations between CCND1 amplification and overexpression with clinicopathological features and patients' outcome in invasive breast cancer; (3) to define the prevalence and clinical significance of cyclin D1 overexpression and CCND1 amplification in ER positive breast carcinomas (4) to define the prevalence of cyclin D1 overexpression and CCND1 amplification in breast cancers with basal-like immunophenotype. CCND1 amplification and protein expression were assessed on a tissue microarray containing 880 unselected invasive breast cancer cases, by means of chromogenic in situ hybridisation using the Spotlight CCND1 amplification probe and immunohistochemistry, using the rabbit monoclonal antibody SP4. A total of 59/613 tumours (9.6%) showed CCND1 amplification and 224/514 (43.6%) showed strong cyclin D1 expression. A strong positive correlation between CCND1 amplification and higher levels of cyclin D1 expression was found (P < 0.001). Basal-like cancers showed infrequent CCND1 amplification and cyclin D1 overexpression (P < 0.001). Both CCND1 amplification and cyclin D1 expression were associated with positive ER status. CCND1 gene amplification was an independent prognostic factor for patients with ER positive breast cancer. Our results demonstrate a strong correlation between CCND1 amplification and its protein expression in breast cancer. However, protein expression is more pervasive than gene amplification and associated with ER expression.