c-erbB-2 Oncoprotein immunoreactivity in gallbladder and biliary tract cancers

Overexpression of c-erbB-2 protein, a 185-kD transmembrane tyrosine kinase protein, is found in a number of human cancers. c-erbB-2 expression was examined, using immunohistochemistry with the polyclonal antibody NCL-PC11 in carcinoma of the gallbladder (n = 13), biliary tract (n = 6), and ampulla of Vater (n = 9). These were compared with nonmalignant conditions such as chronic cholecystitis (n = 11), gallbladder dysplasia (n = 3), and adenoma (n = 1), and ampullary carcinoma in situ (n = 3) and adenoma (n = 1). Most gallbladder carcinomas (85%) and dysplasias (100%), common bile duct (83%) and ampullary (67%) carcinoma, and ampullary carcinoma in situ (67%) showed moderate to strong c-erbB-2 protein immunoreactivity. In contrast, the majority of cases of chronic cholecystitis (64%) had absent or weak c-erbB-2 protein immunostaining. However, immunohistologic detection of c-erbB-2 overexpression in the form of distinct cell membrane immunostaining was found in a minority of gallbladder carcinomas (23%) and not in any of the other pre-neoplastic or neoplastic lesions of the biliary tract or chronic cholecystitis. The patients who had carcinoma with c-erbB-2 overexpression had a shorter median survival period (3.1 months). However, there was no correlation between tumor stage and c-erbB-2 expression. This may be related to the small number of cases of gallbladder tumors available for this study, and further work with a larger series with adequate clinical follow-up time may be required to confirm the prognostic trend. The differences in c-erbB-2 expression between gallbladder, common bile duct, and ampullary carcinomas suggest that mutation of the gene may be a late event in the sequential development of gallbladder and biliary tract cancers.