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Mammalian cell-cycle progression is regulated by the combined action of cyclins/cyclin-dependent kinases (cdks) and cdk inhibitors. Abnormal expression as well as interaction of these proteins may result in malignant transformation of cells. To further address alterations and roles of these cell-cycle proteins in the development of epithelial ovarian carcinomas, we analyzed the expression of the p27 kip1 , cyclin D1, cyclin E, and cdk2. A panel of 79 epithelial ovarian tumors was selected. Immunohistochemical staining of serial paraffin sections was performed using antibodies to p27 kip1 , cyclin D1, cyclin E, and cdk2. The results showed that p27 kip1 and cyclin D1 were concurrently expressed in epithelial ovarian tumors, and the expression was down-regulated in ovarian carcinomas. There was an inverse relationship between the expression level of p27 kip1 and cyclin D1 and the histological tumor grades. On the other hand, the expression of cyclin E and cdk2 was enhanced in ovarian carcinomas. The results suggest that low expression of p27 kip1 and cyclin D1 as well as high expression of cyclin E and cdk2 promotes the development of ovarian tumors. p27 kip1 and cyclin D1 expression are negatively correlated with the malignant degree of epithelial ovarian tumors. Thus, the ovarian tumors with high p27 kip1 and cyclin D1 expression may generally have a somewhat better prognosis, while those with low p27 kip1 and cyclin D1 expression may have a worse prognosis.

Objectives. The aim of this study was to elucidate the expression and the correlation of two cell cycle regulators, cdk4 and its inhibitor p16, in a series of benign, borderline, and malignant ovarian tumors and to evaluate whether their alterations correlate with clinicopathologial parameters and patients' prognosis in epithelial ovarian carcinomas. Methods. Immunohistochemical analysis using anti-cdk4 and anti-p16 antibodies was carried out for 103 paraffin sections of ovarian tumors, and Western blot analysis and cdk4 activity assay were performed in 26 fresh ovarian tumor samples. Results. The results of immunohistochemistry showed that 60.61 and 69.70% of 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 relationship between cdk4 and p16 expression was found. The loss of p16 expression 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 significant effects on overall survival by the Kaplan–Meier method. When the combined phenotypes of the two proteins were analyzed, patients with cdk4-positive/p16-negative expression had a reduced overall survival than other phenotypes 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 carcinomas. The combined phenotypes of cdk4 and p16 proteins could provide a useful prognostic indicator for patients with epithelial ovarian carcinoma.