Frequent loss of expression of the cyclin-dependent kinase inhibitor p27 in epithelial ovarian cancer

Abstract

p27Kip1 is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of tumors, including breast, colon, prostate, and lung carcinomas. In the present study, p27 protein expression was investigated by immunohistochemistry and Western blot analysis in a series of 82 epithelial ovarian tumors [16 classified as low malignant potential (LMP) and 66 classified as primary ovarian adenocarcinomas]. Immunohistochemical analysis revealed frequent loss of p27 expression in primary ovarian adenocarcinomas (33%), with respect to LMP tumors (6%; P = 0.0009). In addition to nuclear staining, cytoplasmic localization of p27 was noted in 45 (55%) of 82 cases. p27 levels inversely correlated with cdk2 kinase activity in a representative subset of tumors. When the clinical outcome of the patients was evaluated in relationship to p27 status, we observed a significant correlation between presence of p27 staining and a longer time to progression (P = 0.032 by log-rank test). These data indicate that loss of p27 is a frequent event in ovarian carcinomas as compared with LMP tumors, suggesting that these tumor types may have different pathogenesis. p27 levels may also represent a useful prognostic marker for predicting disease recurrence in primary ovarian carcinomas.