IMMUNOHISTOCHEMICAL LOCALIZATION OF P21(WAF1) (CIP1) IN NORMAL, HYPERPLASTIC, AND NEOPLASTIC UTERINE TISSUES/

p21(WAF1/CIP1) is nuclear protein that binds to cyclin-dependent kinas e complexes (CDKs) and inhibits the activity of multiple kinases. Thes e CDKs are involved in the regulation of cell cycle progression at sev eral checkpoints. Iu this study, the authors have analyzed by immunohi stochemistry the expression of p21(WAF1/CIP1) in normal uterine tissue s, 12 endometrial hyperplasias, 17 endocervical adenocarcinomas, and 3 1 endometrial adenocarcinomas. In addition, a group of 10 leiomyomas a nd 10 uterine leiomyosarcomas were also stained. To evaluate cell prol iferation, the monoclonal antibody Ki-67 was used In all of the availa ble cases. Terminally differentiated epithelial endocervical and endom etrial cells showed variable expression of p21(WAF1/CIP1), whereas the endometrial hyperplasias, and endocervical and endometrial adenocarci nomas showed decreased expression or were negative. All of the cases o f cervical squamous dysplasia were positive. Normal smooth muscle cell s and 50% of leiomyomas mere negative, whereas all leiomyosarcomas sho wed expression of p21(WAF1/CIP1). These results indicate that p21(WAF1 /CIP1) contributes to differentiation iu normal endometrial and endoce rvical glands. The decreased expression of p21(WAF1/CIP1) in endometri al hyperplasias and carcinomas may be important La the process of neop lastic transformation. The role of certain CDK inhibitors, such as p21 (WAF1/CIP1), is different ent in epithelial and mesenchymal tumorigene sis in the uterus. Copyright (C) 1997 by W.B. Saunders Company.