CELL PROLIFERATION-ASSOCIATED PROTEINS IN ENDOMETRIAL CARCINOMAS, INCLUDING PAPILLARY SEROUS AND ENDOMETRIOID SUBTYPES

Cyclin dependent kinases (cdks) and cyclins regulate the progression o f cells through the cell cycle and can be overexpressed in human cance rs. The purpose of this study was to evaluate the immunohistochemical profile of these proliferation-associated proteins and correlate the r esults with clinicopathologic parameters of endometrial carcinomas. Ar chival tissue sections from 91 endometrial carcinomas were immunostain ed using monoclonal antibodies against p34(CDC2) cdk, cyclins A and B1 , p120, Ki-67, and PCNA. Immunoreactivity was semiquantitatively asses sed and the results correlated with pathologic features and survival. Of the 91 endometrial carcinomas, 74 were endometrioid (17 villoglandu lar, 57 of usual type) and 17 were papillary serous carcinomas. The po sitivity rates for the different proteins in papillary serous and endo metrioid tumors, respectively, were as follows: p34(CDC2), 24% and 23% ; cyclin A, 71% and 64%; cyclin B1, 24% and 26%; p120, 47% and 9%; Ki- 67, 82% and 64%; and PCNA, 47% and 47%. Only p120 correlated with hist ologic tumor type with significantly higher expression in both papilla ry serous and villoglandular endometrioid carcinomas compared to nonvi lloglandular endometrioid carcinomas (p = 0.0001). p120 positivity als o correlated with advanced tumor stage (p = 0.0001). Ki-67, cyclin A, and PCNA correlated with patient survival in endometrioid carcinomas o n univariate analysis (p = 0.01, 0.02, and 0.003, respectively), but, on multivariate analysis, only tumor grade (p = 0.02) and depth of inv asion (p = 0.04) were independent predictors of outcome. In summary, a lthough most of the cell proliferation-associated proteins studied did not appear to be associated with clinicopathologic features of endome trial carcinoma, there was significantly higher expression of p120 in papillary serous and villoglandular endometrioid carcinomas compared t o nonvilloglandular endometrioid carcinomas, suggesting a possible rol e of p120 in tumor behavior. In addition, Ki-67, cyclin A, and PCNA ex pression correlated with survival in endometrioid carcinoma, but only in a univariate analysis.