@@iCCND1@ amplification and cyclin D1 expression in breast cancer and their relation with proteomic subgroups and patient outcome

• Published in: Breast cancer research and treatment 2008-05, Vol.109 (2), p.325-335
• Main Authors: Elsheikh, Somaia, Green, Andrew R, Aleskandarany, Mohammed A, Grainge, Matthew, Paish, Claire E, Lambros, Maryou BK, Reis-Filho, Jorge S, Ellis, Ian O
• Format: Article
• Language: English
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-007-9659-8

Introduction: Despite strong evidence regarding the role of @@iCCND1@ amplification and protein overexpression in breast carcinoma, the associations between @@iCCND1@ amplification/cyclin D1 overexpression and clinicopathological variables and clinical outcome remain controversial. Aims of the study: (1) to correlate cyclin D1 expression with gene amplification; (2) to analyse the correlations between @@iCCND1@ 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 @@iCCND1@ amplification in ER positive breast carcinomas (4) to define the prevalence of cyclin D1 overexpression and @@iCCND1@ amplification in breast cancers with basal-like immunophenotype. Materials and methods: @@iCCND1@ 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 @@iCCND1@ amplification probe and immunohistochemistry, using the rabbit monoclonal antibody SP4. Results: A total of 59/613 tumours (9.6%) showed @@iCCND1@ amplification and 224/514 (43.6%) showed strong cyclin D1 expression. A strong positive correlation between @@iCCND1@ amplification and higher levels of cyclin D1 expression was found (@@iP@ < 0.001). Basal-like cancers showed infrequent @@iCCND1@ amplification and cyclin D1 overexpression (@@iP@ < 0.001). Both @@iCCND1@ amplification and cyclin D1 expression were associated with positive ER status. @@iCCND1@ gene amplification was an independent prognostic factor for patients with ER positive breast cancer. Conclusion: Our results demonstrate a strong correlation between @@iCCND1@ amplification and its protein expression in breast cancer. However, protein expression is more pervasive than gene amplification and associated with ER expression.