DETERMINATION OF THE PROGNOSTIC VALUE OF CYCLIN D1 OVEREXPRESSION IN BREAST-CANCER

Cyclin D1 plays a critical role in the timing of the initiation of DNA synthesis in the normal cell cycle of mammalian cells, Deregulated ex pression of this protein has been seen in a variety of tumours either as a result of gene amplification or chromosomal translocation, in bre ast cancer and B cell malignancies respectively. In order to determine the role this putative oncoprotein plays in breast cancer, we have ap plied a new monoclonal antibody, recently produced in our laboratory, in an imnunohistochemical study of 93 primary breast carcinomas. We sh ow that approximately 28% of the cases displayed enhanced expression o f the cyclin D1 protein. Furthermore, either cyclin D1, cyclin D3, or both, were expressed in 69% of cases, suggesting that overexpression o f any one member of this family may relieve cancer cells of their mito genic stimulatory requirement. In addition, we show that those patient s whose breast cancers co-express cyclin D1 with either epidermal grow th factor receptor (EGFR) or the retinoblastoma protein (pRB) have a s ignificantly poorer prognosis in comparison to those expressing cyclin D1 alone. Our observations indicate that, in a subset of breast cance rs, aberrant cyclin D1 expression is a contributory factor to tumorige nesis and in association with EGFR or pRB expression, identify those t umours which may require more aggressive therapy.