Cell proliferation-associated proteins in endometrial carcinomas, including papillary serous and endometrioid subtypes.
Cyclin dependent kinases (cdks) and cyclins regulate the progression of cells through the cell cycle and can be overexpressed in human cancers. The purpose of this study was to evaluate the immunohistochemical profile of these proliferation-associated proteins and correlate the results with clinicopathologic parameters of endometrial carcinomas. Archival tissue sections from 91 endometrial carcinomas were immunostained using monoclonal antibodies against p34CDC2 cdk, cyclins A and B1, p120, Ki-67, and PCNA. Immunoreactivity was semiquantitatively assessed and the results correlated with pathologic features and survival. Of the 91 endometrial carcinomas, 74 were endometrioid (17 villoglandular, 57 of usual type) and 17 were papillary serous carcinomas. The positivity rates for the different proteins in papillary serous and endometrioid tumors, respectively, were as follows: p34CDC2, 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 histologic tumor type with significantly higher expression in both papillary serous and villoglandular endometrioid carcinomas compared to nonvilloglandular endometrioid carcinomas (p = 0.0001). p120 positivity also correlated with advanced tumor stage (p = 0.0001). Ki-67, cyclin A, and PCNA correlated with patient survival in endometrioid carcinomas on univariate analysis (p = 0.01, 0.02, and 0.003, respectively), but, on multivariate analysis, only tumor grade (p = 0.02) and depth of invasion (p = 0.04) were independent predictors of outcome. In summary, although most of the cell proliferation-associated proteins studied did not appear to be associated with clinicopathologic features of endometrial carcinoma, there was significantly higher expression of p120 in papillary serous and villoglandular endometrioid carcinomas compared to nonvilloglandular endometrioid carcinomas, suggesting a possible role of p120 in tumor behavior. In addition, Ki-67, cyclin A, and PCNA expression correlated with survival in endometrioid carcinoma, but only in a univariate analysis.
Kallakury
B V
BV
Department of Pathology, Albany Medical College, NY 12208, USA.
Ambros
R A
RA
Hayner-Buchan
A M
AM
Sheehan
C E
CE
Malfetano
J H
JH
Ross
J S
JS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D016203:CDC2 Protein Kinase / Q000032:analysis; D018269:Carcinoma, Endometrioid / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D019925:Cyclin A / Q000032:analysis; D019926:Cyclin B / Q000032:analysis; D056744:Cyclin B1; D018844:Cyclin-Dependent Kinases / Q000032:analysis*; D016213:Cyclins / Q000032:analysis*; D018283:Cystadenocarcinoma, Papillary / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D015996:Survival Rate; D012359:tRNA Methyltransferases
D000911:Antibodies, Monoclonal; C534699:CCNB1 protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D016213:Cyclins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; C065028:NOP2 protein, human; D012359:tRNA Methyltransferases; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases