CLINICAL IMPORTANCE OF P53 PROTEIN IN GALL-BLADDER CARCINOMA AND ITS PRECURSOR LESIONS

Aims-To study the expression and importance (if any) of p53 protein in gall bladder carcinoma and its precursor lesions. Methods-Immunohisto chemical staining was performed on formalin fixed, paraffin wax embedd ed histological sections with an anti-human p53 monoclonal antibody (D O-7; Dako Corporation M7001) (24 carcinomas, one adenocarcinoma in sit u, six dysplasias, three adenomas and four cases of chronic cholecysti tis). Invasive, in situ, and dysplastic areas as well as normal-lookin g epithelium were sought. Nuclear staining was assessed according to i ntensity and extent of positive cells. Both variables were graded on a scale of 1-3 and aggregate p53 scores were obtained (range: 0, 2-6). Only p53 scores of greater than or equal to 3 were regarded as signifi cant. Results-Clinically important amounts of p53 were expressed in 92 % of invasive carcinomas, 86% of carcinoma in situ, and 28% of dysplas tic areas. None of the adenomas contained clinically important amounts of p53. Normal epithelium, present ire all the cases, did not express p53 except in one case of moderately differentiated adenocarcinoma (p 53 score 3). In general, there was no difference in the prevalence of p53 protein expression between dysplasias associated with, and those u nassociated with invasive disease. There was a tendency for higher gra de carcinomas to express more p53 protein. Conclusions-The distributio n of p53 protein in invasive carcinomas and the adjacent dysplastic an d preinvasive lesions suggests that it is more commonly expressed than previously thought. The fact that p53 protein is also expressed in ca ses of dysplasia and carcinoma in situ unassociated with invasive mali gnancy lends further support to the contention that p53 gene mutations may have a role in the pathogenesis of gall bladder cancer. Expressio n of p53 protein may possibly be an indication of likely disease progr ession from dysplasia, to carcinoma in situ, to invasive disease.