The p16-cyclin D1/CDK4-pRb pathway and clinical outcome in epithelial ovarian cancer

A significant positive association has been reported between p16 expression and clinical outcome for epithelial: ovarian cancer patients. However, there is a reciprocal correlation between genetic alterations of single members of the p16-cyclin D1/CDK4-pRb pathway (G(1) pathway). Simultaneous evaluation of these four elements may produce a better prognostic factor than p16 alone, We studied the prognostic significance of the G(1) pathway in 59 epithelial ovarian cancer patients undergoing surgery and platinum-based chemotherapy by immunohistochemical technique. Abnormal expression of p16 or pRb was defined by negative nuclei staining, and that of CDK4 and cyclin D1 was defined by 50% nuclear staining. An abnormal G(1) pathway was indicated in cases that have at least one abnormality among these four elements, Abnormal expression of p16, pRb, and cyclin D1/CDK4 was observed in 33.9, 3.4, and 15.3% of studied cases, respectively. Abnormal G(1) pathway was detected in 49.2% (29 of 59) of all cases. The patients with normal G(1) pathway tended to achieve a higher complete response rate (81.0%) to chemotherapy, compared with patients with abnormal G(1) pathway (55.0%); however, there was no significant difference (P = 0.1001) between the two groups. Univariate analyses identified advanced stage [hazards ratio (HR), 3.665; P = 0.0218], histological low grade (HR, 3.625; P = 0.0066), and abnormal G(1) pathway (HR, 2.935; P = 0.03) as prognostic factors for overall survival. The G(1) pathway might help as a prognostic factor to select high-risk patients.