Expression and Subcellular Localization of the Cyclin-Dependent Kinase Inhibitor p27Kip1 in Epithelial Ovarian Cancer

Objective. To determine if p27Kip1 expression was altered in epithelial ovarian cancers as compared to normal ovarian surface epithelial (NOSE) cells and to determine if subcellular localization of p27Kip1 was an important feature. Methods. Thirteen tumor samples (1 Stage IC [early] and 12 Stage III/IV [advanced]) from patients with epithelial ovarian cancer and five NOSE samples were evaluated. Samples were surgically dissected to obtain an enriched population (90%) of cancer cells. The level of p27Kip1 protein expression was determined by Western blot analysis. Actin was used as a loading control, and results were quantified by scanning densitometry using the ratio of the p27Kip1 signal to the actin signal for comparison. To evaluate the subcellular localization of p27Kip1, immunocytochemical staining was performed. Clinical pathological parameters were correlated to nuclear p27Kip1 staining to establish if any association existed. Results. When comparing the expression of p27Kip1 between NOSE and ovarian cancer samples, only 2 of 13 ovarian cancer samples had altered p27Kip1 expression. No correlation was found between the expression level of p27Kip1 on Western blot and clinical pathological correlates. While no correlation between expression level of p27Kip1 and subcellular localization was found, decreased nuclear staining (1+) was associated with shorter survivals using the log-rank test (P < 0.001). More importantly, in all tumor samples examined under the microscope, no nuclear p27Kip1 staining was noted in cells that were undergoing mitosis. Conclusions. p27Kip1 protein degradation may not be modified in ovarian cancer cells undergoing mitosis. Altered expression of p27Kip1 is not an overwhelming feature in certain epithelial ovarian cancers. Decreased nuclear staining of p27Kip1 is associated with poor survival in some epithelial ovarian cancers.