Enhanced cell kinetics, p53 accumulation and high p21WAF1 expression in chronic cholecystitis: comparison with background mucosa of gallbladder carcinomas

AIMS: Since neoplasia resulting from chronic inflammation has recently attracted increasing attention, we have investigated surgically removed gallbladders to examine the relationship between chronic cholecystitis and carcinogenesis. METHODS AND RESULTS: The mucosa of 108 cholecystectomy specimens without gallbladder cancer and 54 surgically resected gallbladder carcinomas were classified into three groups according to the degree of lymphocytic infiltration, and assessed immunohistochemically for Ki67, p53, p21WAF1 and apoptosis. In gallbladder mucosa without carcinoma, all four parameters tended to increase with the inflammation score (IS). Significantly positive correlations were revealed between Ki67 and p53, Ki67 and p21WAF1, and p53 and p21WAF1. However, in gallbladder carcinoma cases, values of p53 and p21WAF1 for background mucosa were elevated as compared to the mucosa of cholecystitis with low IS, but there was no correlation between their expression and IS, except for Ki67. CONCLUSIONS: Severe chronic cholecystitis is associated with acceleration of epithelial cell turnover, damaged cells being eliminated by apoptosis. The background mucosa of gallbladder carcinomas showed similar cell proliferative activity (Ki67) to that in cholecystitis, with no parallel changes of p53 and p21WAF1 expression, suggesting the possibility of unknown cofactors causing genomic damage.