Ras p21 protein immunoreactivity and its relationship to p53 expression and prognosis in gallbladder and extrahepatic biliary carcinoma.

Ras oncogene mutation is found in many human malignancies. The ras family of genes consists of three functional genes which encode highly similar, guanine nucleotide-binding, proteins (p21) of 21kDa, with GTPase activity. The p21 protein is present on the inner aspect of the plasma membrane of a variety of cells. Using a polyclonal antibody, pan-ras p21 (Oncogene Science), the immunohistochemical expression of the ras oncogene in human gallbladder adenocarcinoma (n = 13) and dysplasia (n = 3), chronic cholecystitis (n = 11), common bile duct carcinoma (n = 6), together with ampullary carcinoma (n = 8) and carcinoma in situ (CIS) (n = 3), was examined. A statistically significant difference in ras p21 immunoreactivity between gallbladder cancers and chronic cholecystitis (P = 0.032; chi 2 test) was demonstrated. Strong ras p21 immunoreactivity was present in most gallbladder carcinomas (n = 8; 62%) but not in the cases of gallbladder dysplasia (n = 1; 33%) or chronic cholecystitis (n = 2; 18%). However, the ras p21 expression was strong in only a minority of the cases of ampullary carcinoma (n = 1; 13%), common bile duct carcinomas (n = 3; 50%), and none of the ampullary CIS, and was not shown to be statistically significant. There was no statistically significant correlation between ras p21 expression and patient survival (r = 0.18, r2 = 0.031, P = 0.56; simple regression analysis), or between ras p21 expression and p53 immunoreactivity (r = 0.13, r2 = 0.017, P = 0.47; simple regression analysis). In conclusion, ras p21 expression is increased in most cases of gallbladder carcinomas with no specific relationship to tumour grade suggesting that it may be important in the development of gallbladder carcinomas but not in its progression. No significant correlation was found between ras p21 expression and p53 immunoreactivity in gallbladder and biliary tract tumours and ras p21 immunoreactivity does not appear to be of any prognostic value. The lower rate of ras p21 overexpression in common bile duct and ampullary carcinomas suggests that these tumours may have a different molecular origin to gallbladder cancers.