Differences in c-fos gene product expression in cancers of the gall-bladder and biliary tract

The c-fos gene encodes a 55 kDa nuclear protein product that complexes to a cellular protein, p39. The pattern of expression of c-fos is particularly complex with increased expression of the protein observed in undifferentiated cultured cells while reduced expression is found during terminal differentiation. The expression of c-fos gene was studied by immunohistochemistry in carcinoma of the gall-bladder (n = 13), biliary tract (n = 5) and ampulla of Vater (n = 9). Non-malignant conditions investigated include chronic cholecystitis (n = 11), gall-bladder dysplasia (n = 3) and adenoma (n = 1), and ampullary carcinoma in situ (n = 3). Strong positive granular cytoplasmic immunostaining for c-fos oncoprotein was present in most gall-bladder adenocarcinomas (n = 11; 85%). The single gall-bladder adenoma and only one of the dysplasia cases were positive. Most of the cases of chronic cholecystitis showed either absent or only focal to patchy and weak to moderate c-fos immunoreactivity in the deeper glands and Rokitansky-Aschoff sinuses but not in the superficial epithelium. None of the biliary tract and ampullary tumors showed immunostaining for c-fos. The difference in c-fos immunoreactivity between gall-bladder carcinoma and chronic cholecystitis was statistically significant (P = 0.0002; chi 2 test with continuity correction). In conclusion, c-fos protein may be important in the development of gall-bladder neoplasia with increased c-fos immunoreactivity in gall-bladder carcinoma but not in chronic cholecystitis, biliary tract and ampullary neoplasms. These findings suggest that gall-bladder carcinoma may arise from a different genetic basis compared to biliary tract and ampullary cancers.