Implication of malignancy and prognosis of p27(kip1), cyclin E, and Cdk2 expression in epithelial ovarian tumors

Objective. The aim of this study was to further evaluate whether the expres sion of p27(kip1), cyclin E, and cdk2 is related to the malignancy of ovari an tumors and whether their expressions, alone or in combination, are assoc iated with prognosis in epithelial ovarian carcinoma. Methods. Immunohistochemical analysis using anti-p27(kip1), anti-cyclin E, and anti-cdk2 antibodies was carried out for 103 cases consisting of benign , borderline, and malignant ovarian tumors, and Western blot analysis and c dk2 activity assay were performed in 26 fresh ovarian tumor samples. Results. p27(kip1) expression was reduced in ovarian carcinomas in contrast to benign and borderline tumors. The expression of cyclin E and cdk2 gradu ally increased from benign to borderline to malignant tumors. Kaplan-Meier survival analysis showed that patients with p27(kip1) expression had a high overall survival rate. Patients with cyclin E overexpression had a low ove rall survival rate. When the combination of these proteins was analyzed, pa tients with the p27(kip1) (-)/cyclin E (++)/cdk2 (++) phenotype were signif icantly associated with the poorest overall survival. In multivariate Cox r egression analysis, the combined phenotype of p27(kip1) (-)/cyclin E (++)/c dk2 (++) was independently related to poor prognosis. Conclusions. Our results suggest that loss of p27(kip1) expression and over expression of cyclin E or cdk2 were significantly associated with malignanc y in ovarian tumors. p27(kip1) and cyclin E proteins may be valuable progno stic factors for epithelial ovarian carcinoma patients. Furthermore, the co mbined evaluation of p27(kip1) /cyclin E/cdk2 may provide the most importan t prognostic implication. (C) 2001 Academic Press.