IMMUNOHISTOCHEMICAL ANALYSIS OF THE EXPRESSION OF CDK4 AND P16(INK4) IN HUMAN ENDOMETRIOID-TYPE ENDOMETRIAL CARCINOMA

BACKGROUND, Abnormalities in G1 cell cycle regulation have been associ ated with the malignant transformation of cells. To obtain further inf ormation about the role of factors regulating the G1 cell cycle in the development of endometrial carcinoma, the authors analyzed the expres sion of cdk4 (cyclin-dependent kinase) and p16(INK4) (an inhibitor of cdk4). METHODS. Immunohistochemical staining was performed on 20 speci mens of normal endometria and 41 specimens of endometrioid-type endome trial carcinoma using antibodies against cdk4 and p16(INK4). RESULTS. In the glandular epithelia of the normal endometria, cytoplasmic stain ing of cdk4 and p16(INK4) was observed only in the proliferative phase , but nuclear staining of these agents was negligible. In endometrial carcinomas, 8 (19.5%) and 14 (34.2%) were positive for cdk4 and p16(IN K4) in the nucleus, respectively. Topographically, the nuclear cdk4 po sitive tumor cells were negative for p16(INK4) and the nuclear p16(INK 4) positive tumor cells were found in areas without nuclear cdk4 expre ssion, suggesting an inverse correlation between the two agents. In ad dition, the poorly differentiated carcinomas were more frequently posi tive for nuclear cdk4 than were the highly differentiated carcinomas ( P = 0.03). CONCLUSIONS, These data suggest that increased expression o f nuclear cdk4 associated with loss of p16(INK4) expression could be i nvolved in the carcinogenesis of a subset of endometrial carcinomas. ( C) 1997 American Cancer Society.