Correlation of C-erbB-2 Oncogene Amplification by Chromogenic in situ Hybridization and Expressions of Cell Cycle Regulatory Proteins in Infiltrating Duct Carcinoma of the Breast

ABSTRACT

PURPOSE: Gene amplification and/or over-expression of the c-erbB-2 are linked with poor prognosis in breast cancer. There has been only a few reports about the connection of c-erbB-2 oncogene amplification with cell regulatory proteins such as p27(kip1), cyclin D1, Rb, and E2F-1. The purpose of this study is to determine the correlation the amplification of the c-erbB-2 oncogene and protein expressions of p27(kip1), cyclin D1, Rb, and E2F-1. METHODS: Using Chromogenic in situ Hybridization (CISH) the amplification the c-erbB-2 oncogene were determined from paraffin sections of 48 infiltrating duct carcinomas (IDC). The protein expressions of p27(kip1), cyclin D1, Rb, and E2F-1 were studied immunohistochemically. RESULTS: Among the 48 evaluated IDC patients, amplifications of the c-erbB-2 oncogene by CISH were observed in 14 cases (29.1%). The amplification of the c-erbB-2 oncogene showed a significant correlation with tumor size and stage (P=0.0001 and P=0.001). The proteins of p27(kip1), cyclin D1, Rb, and E2F-1 were expressed by IHC in 23 cases (47.9%), 17 cases (35.4%), 27 cases (56.3%), and 22 cases (45.8%), respectively. Down- regulation of protein expressions showed a significant correlation with tumor size (P=0.031) in p27(kip1) and estrogen and progesterone receptor status (P=0.026 and P=0.001) in Rb. The expression of the E2F-1 protein showed a significant correlation with tumor size, stage, and histologic grade (P=0.003, P=0.030, and P=0.036). The amplification of the c-erbB-2 oncogene between down-regulation of p27(kip1) protein and E2F-1 protein showed a statistically significant correlation. CONCLUSION: The amplification of the c-erbB-2 oncogene may be correlation with cell cycle regulatory proteins such as p27(kip1) and E2F-1.