NUCLEAR OVEREXPRESSION OF P53 PROTEIN DOES NOT CORRELATE WITH GENE MUTATION IN PRIMARY PERITONEAL CARCINOMA

Primary peritoneal carcinoma (PPC) is an aggressive malignancy of the female coelomic epithelium. Previously we had analyzed 29 cases of PPC for p53 protein accumulation by immunocytochemistry. P53 was overexpr essed in 83% (24 of 29) of PPCs, including 21 tumors with diffuse inte nse staining of 100% of tumor nuclei and three additional tumors with significant focal staining. Here we report results of a mutational ana lysis on the entire p53 coding sequence of 22 of these cases (comprisi ng 18 p53-positive and four negative tumors), using single-strand conf ormation polymorphism (SSCP) and direct sequence analysis. Only 2 of 2 2 (9%) patients harbored a p53 mutation (which, interestingly, were id entical and consisted of a codon 259 Asp --> His exchange), despite di ffuse overexpression of high levels of nuclear p53 protein in most cas es. This result indicates that (1) the abnormal p53 expression is usua lly not caused by mutations of the p53 gene in PPC and (2) PPC is part of a growing number of tumors that share evidence of p53 dysfunction in the absence of mutation. Copyright (C) 1997 by W.B. Saunders Compan y.