OVEREXPRESSION OF P53 PROTEIN IN ADENOCARCINOMA OF THE PANCREAS

Mutations in the p53 tumor suppressor gene are frequently identified i n human neoplasms. These mutations may be associated with stabilizatio n and, therefore, with overexpression of the p53 protein product as de termined by immunohistochemical staining. Using a new antigen retrieva l method and a polyclonal antibody to p53 (CM-1), the authors examined 48 formalin-fixed paraffin-embedded adenocarcinomas of the pancreas f or overexpression of the p53 gene product. These 48 carcinomas were ob tained from a series of patients with well-documented clinical histori es and extensive follow-up. The carcinomas had been analyzed previousl y for K-ras gene mutations, tumor ploidy, and tumor proliferating inde x. Specific diffuse nuclear staining for the p53 protein was identifie d in 19 of the 48 (40%) infiltrating carcinomas examined. Focal or neg ative staining was seen in the remaining 29 cases (60%). In addition, 17 of the neoplasms contained synchronous in situ carcinomas; two (12% ) of these displayed diffuse nuclear staining for the p53 protein. Ove rexpression of p53 was associated with aneuploidy (P=.05), which had b een a poor prognosticator in this series of adenocarcinomas of the pan creas. Although overexpression of p53 appeared to be associated with p oor prognosis (hazard ratio, 1.8; P=.07), this was not statistically s ignificant. Overexpression of p53 was not significantly associated wit h K-ras oncogene mutations or tumor proliferating index. The authors c onclude that overexpression of the p53 protein occurs frequently in in vasive adenocarcinomas of the pancreas and in some in situ carcinomas, as well.