Expression of the p53 Induced Tumor Suppressor p21waf1/cip1 in Ovarian Carcinomas

Mutations of the p53 gene are the most common genetic alteration in malignant human tumors, including ovarian carcinomas of surface epithelial origin. A cyclin-dependent kinase inhibitor, p21waf1/cip1, is thought to be an important mediator of p53-induced cell cycle arrest. Although numerous studies have reported p53 expression and mutation in ovarian tumors, none have correlated p53 expression with that of its downstream effector, p21waf1/cip1. We studied p53 and p21waf1/cip1 expression by immunohistochemistry in 44 ovarian carcinomas of different histologic types and correlated these findings with each other and with proliferation as measured by expression of the Ki-67 nuclear antigen. Fifty percent of tumors expressed p53, whereas 34% expressed p21waf1/cip1. Clear cell carcinomas expressed p21waf1/cip1 significantly more often than other histologic types, and tumors with squamous differentiation showed higher p21waf1/cip1 expression in these areas. There was no correlation of p21waf1/cip1 expression with p53 expression, p53 mutation, or Ki-67 expression. p21waf1/cip1 appears to be induced independently of p53 in these tumors and may be associated with differentiation rather than proliferation.