Expression of p53 in adenocarcinoma of the gallbladder and bile ducts

Abstract: Point mutation of the p53 tumor suppressor gene appears to be an important event in tumor development and progression, and overexpression of the p53 gene product has been widely studied in a variety of neoplasms. Some point mutations of the p53 gene lead to an increase in half-life in the gene product, which accumulates in the nucleus and can be detected by immunohistochemical means. We studied overexpression of p53 protein in specimens from 12 patients with adenocarcinoma of the gallbladder, two gallbladders with epithelial dysplasia without carcinoma, eight carcinomas of the common bile duct, 13 hilar cholangiocarcinomas, and six peripheral cholangiocarcinomas. The monoclonal antibody Ab-2 (Oncogene Science) was used in conjunction with citrate microwave antigen retrieval. Nuclear staining was scored as positive (graded 1 to 3, depending on number of positive nuclei) or negative. Overexpression of p53 protein was present in 7/12 (58%) gallbladder carcinomas, and was seen more often in moderately or poorly differentiated tumors. Intramucosal carcinoma adjacent to invasive carcinoma was positive in three cases, although fewer cells stained than in the carcinoma. Two cases of low-grade dysplasia not associated with carcinoma were negative. Expression of p53 was not an independent prognostic factor when survival was related to grade and stage of tumor. Three of eight (38%) common bile duct carcinomas and 5/13 (38%) hilar cholangiocarcinomas were positive for p53. Slightly fewer (2/6, 33%) peripheral cholangiocarcinomas were positive. No difference in survival relative to p53 expression was demonstrated.