Immunohistochemical localization of p21(WAF1/CIP1) in normal, hyperplastic, and neoplastic uterine tissues

p21(WAF1 CIP1) is a nuclear protein that binds to cyclin-dependent kinase complexes (CDKs) and inhibits the activity of multiple kinases. These CDKs are involved in the regulation of cell cycle progression at several checkpoints. In this study, the authors have analyzed by immunohistochemistry the expression of p21(WAF1 CIP1) in normal uterine tissues, 12 endometrial hyperplasias, 17 endocervical adenocarcinomas, and 31 endometrial adenocarcinomas. In addition, a group of 10 leiomyomas and 10 uterine leiomyosarcomas were also stained. To evaluate cell proliferation, the monoclonal antibody Ki-67 was used in all of the available cases. Terminally differentiated epithelial endocervical and endometrial cells showed variable expression of p21(WAF1 CIP1), whereas the endometrial hyperplasias, and endocervical and endometrial adenocarcinomas showed decreased expression or were negative. All of the cases of cervical squamous dysplasia were positive. Normal smooth muscle cells and 50% of leiomyomas were negative, whereas all leiomyosarcomas showed expression of p21(WAF1 CIP1). These results indicate that p21(WAF1 CIP1) contributes to differentiation in normal endometrial and endocervical glands. The decreased expression of p21(WAF1 CIP1) in endometrial hyperplasias and carcinomas may be important in the process of neoplastic transformation. The role of certain CDK inhibitors, such as p21(WAF1 CIP1) is different in epithelial and mesenchymal tumorigenesis in the uterus.