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 expression of this protein has been seen in a variety of tumours either as a result of gene amplification or chromosomal translocation, in breast cancer and B cell malignancies respectively. In order to determine the role this putative oncoprotein plays in breast cancer, we have applied a new monoclonal antibody, recently produced in our laboratory, in an immunohistochemical study of 93 primary breast carcinomas. We show that approximately 28% of the cases displayed enhanced expression of the cyclin D1 protein. Furthermore, either cyclin D1, cyclin D3, or both, were expressed in 69% of cases, suggesting that overexpression of any one member of this family may relieve cancer cells of their mitogenic stimulatory requirement. In addition, we show that those patients whose breast cancers co-express cyclin D1 with either epidermal growth factor receptor (EGFR) or the retinoblastoma protein (pRB) have a significantly poorer prognosis in comparison to those expressing cyclin D1 alone. Our observations indicate that, in a subset of breast cancers, aberrant cyclin D1 expression is a contributory factor to tumorigenesis and in association with EGFR or pRB expression, identify those tumours which may require more aggressive therapy.