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 associated with the malignant transformation of cells. To obtain further information about the role of factors regulating the G1 cell cycle in the development of endometrial carcinoma, the authors analyzed the expression of cdk4 (cyclin‐dependent kinase) and p16 INK4 (an inhibitor of cdk4). METHODS Immunohistochemical staining was performed on 20 specimens of normal endometria and 41 specimens of endometrioid‐type endometrial carcinoma using antibodies against cdk4 and p16 INK4 . RESULTS In the glandular epithelia of the normal endometria, cytoplasmic staining 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 INK4 in the nucleus, respectively. Topographically, the nuclear cdk4 positive tumor cells were negative for p16 INK4 and the nuclear p16 INK4 positive tumor cells were found in areas without nuclear cdk4 expression, suggesting an inverse correlation between the two agents. In addition, the poorly differentiated carcinomas were more frequently positive for nuclear cdk4 than were the highly differentiated carcinomas ( P = 0.03). CONCLUSIONS These data suggest that increased expression of nuclear cdk4 associated with loss of p16 INK4 expression could be involved in the carcinogenesis of a subset of endometrial carcinomas. Cancer 1997; 80:2250‐6. © 1997 American Cancer Society.