Inverse expression of cdk4 and p16 in epithelial ovarian tumors

Objectives. The aim of this study was to elucidate the expression and the c orrelation of two cell cycle regulators, cdk4 and its inhibitor p16, in a s eries of benign, borderline, and malignant ovarian tumors and to evaluate w hether their alterations correlate with clinicopathologial parameters and p atients' prognosis in epithelial ovarian carcinomas. Methods. Immunohistochemical analysis using anti-cdk4 and anti-p16 antibodi es was carried out for 103 paraffin sections of ovarian tumors, and Western blot analysis and cdk4 activity assay were performed in 26 fresh ovarian t umor samples. Results. The results of immunohistochemistry showed that 60.61 and 69.70% o f benign, 69.57 and 56.52% of borderline, and 74.47 and 40.43% of malignant tumors expressed cdk4 and p16, respectively, demonstrating increased cdk4 and decreased p16 expression in ovarian carcinomas. A significant inverse r elationship between cdk4 and p16 expression was found. The loss of p16 expr ession was more correlated with G(2) and G(3) tumors in contrast with G(1) tumors. No significant correlation was observed between cdk4 expression and clinicopathological parameters. Neither cdk4 nor p16 expression has signif icant effects on overall survival by the Kaplan-Meier method. When the comb ined phenotypes of the two proteins were analyzed, patients with cdk4-posit ive/p16-negative expression had a reduced overall survival than other pheno types of cdk4/p16. Conclusions. These data suggest that inverse expression of cdk4 and p16 may be involved in the development and progression of epithelial ovarian carci nomas. The combined phenotypes of cdk4 and p16 proteins could provide a use ful prognostic indicator for patients with epithelial ovarian carcinoma. (C ) 2000 Academic Press.