Alteration of Cyclin D1 in Chinese Patients with Breast Carcinoma and its Correlation with Ki-67, pRb, and p53

Abstract

For the female population in Asia, systematic investigation on alterations of cyclin D1 in breast carcinoma is rare, and correlation between cyclin D1 expression with clinicopathological parameters, survival rate, and other prognostic marker associated with cell cycle is unclear. Expression of cyclin D1 protein, Ki-67, pRb, and p53 was determined by immunohistochemistry in 18 cases of early breast carcinomas and 80 cases of invasive ductal carcinomas. Genetic alteration of cyclin D1 gene and overexpression of cyclin D1 mRNA were detected by Southern blot and RT-PCR, respectively. Expression of cyclin D1 is negative in usual ductal hyperplasia (UDH) and atypical ductal hyperplasia (ADH). However, in 52.0% (51/98) of all breast carcinomas, positive expression of cyclin D1 was observed. Five-year survival rate of the patients with positive expression of cyclin D1 (52.7%) is significantly lower than the cases with negative expression of cyclin D1 (72.1%). Positive rate of cyclin D1 protein in invasive ductal carcinoma (52.5%) is slightly higher than overexpression rate (40.8%) of cyclin D1 mRNA but significantly higher than amplification rate of cyclin D1 gene (18.4%). Expression of cyclin D1 is correlated with Ki-67 expression, but not correlated with pRb and p53 expression. Positive expression of cyclin D1 could serve as a poor prognostic marker for Chinese patients with breast carcinoma independent of nodal metastasis and clinical stage. Expression of cyclin D1 protein is affected more directly by overexpression of cyclin D1 mRNA rather than cyclin D1 gene amplification. The cooperation between pRb and p53 with cyclin D1 protein in the carcinogenesis of breast carcinoma is not supported by the results.