The c‐fosgene encodes a 55kDa nuclear protein product that complexes to a cellular protein, p39. The pattern of expression of c‐fosis 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‐fosgene was studied by immuno‐histochemistry 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 insitu(n=3). Strong positive granular cytoplasmic Immunostaining for c‐fosoncoprotein 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‐fosImmunoreactivity 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‐fosimmunoreactivity between gall‐bladder carcinoma and chronic cholecystitis was statistically significant (P=0.0002; χ2test with continuity correction). In conclusion, c‐fosprotein may be important in the development of gall‐bladder neoplasia with increased c‐fosImmunoreactivity in gallbladder carcinoma but not In chronic cholecystitis, biliary tract and ampuliary neoplasms. These findings suggest that gall‐bladder carcinoma may arise from a different genetic basis compared
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