Expression of pRb, p16, Cyclin D1 and Cyclin E in Infiltrating Duct Carcinoma of the Breast

ABSTRACT

BACKGROUND: Inactivation of the retinoblastoma protein (pRb) is a mechanism by which tumor cells can subdue normal growth control. Among the molecules involved in control of pRb phosphorylation, cyclin D1 and cyclin E have been found to be deregulated and overexpressed in various types of cancers. METHODS: Immunohistochemical stains for pRb, p16, cyclin D1 and cyclin E were performed in 73 cases of infiltrating duct carcinomas of the breast. In addition to analysis of their expression rates, the relationships between their expressions and the clinicopathologic parameters were evaluated. RESULTS: pRb, p16, cyclin D1 and cyclin E were positive in 64.7% (44 out of 68 cases), 24.6% (15 out of 61 cases), 43.8% (32 out of 73 cases) and 61.6% (45 out of 73 cases), respectively. Their expression rates were not significantly associated with clinicopathologic prognostic factors. 33 out of 38 cases with p16-negative reactions were pRb positive, while 10 out of 15 cases with pRb-negative reactions were p16 positive. There was a significant inverse relationship between pRb and p16 expressions (P<0.005). 25 out of 32 cases with cyclin E-positive reactions were cyclin D1-positive, and 25 out of 45 cases with cyclin D1-positive reactions were cyclin E-positive. A statistically significant association was observed between cyclin D1 and cyclin E expressions (P<0.05). CONCLUSIONS: The main mechanism during tumorigenesis of breast carcinoma depends on the cyclin D1/p16/pRb pathway, but cyclin E might play a role in the absence of cyclin D1. The inverse correlation between the pRb and p16 expressions may represent one of the important mechanisms in tumorigenesis, as well.