Increased cell proliferation and transforming growth factor-alpha (TGF alpha) in the gall-bladder epithelium of patients with pancreaticobiliary maljunction

Pancreaticobiliary maljunction is associated frequently with gall-bladder carcinoma, Although increased turnover of the gall-bladder epithelium in patients with pancreaticobiliary maljunction is thought to predispose to carcinogenesis, there is little data to confirm this hypothesis, In addition, no previously published study has addressed the process underlying cell proliferation, In this study, cell kinetics were first evaluated using two methods, proliferating cell nuclear antigen (PCNA) immunohistochemical staining and argyrophilic nucleolar organizer region (AgNOR) staining, Second, immunohistochemistry was used to investigate the expression of transforming growth factor-alpha (TGF alpha), a potential regulator of cell proliferation in the gall-bladder, The gall-bladders of 11 patients with pancreaticobiliary maljunction were studied, and 11 gall-bladders removed from patients during other Surgery were used as controls, The number of PCNA-positive cells and the number of AgNOR per nucleus were significantly greater in the gall-bladders of patients with pancreaticobiliary maljunction than in the control gall-bladders, The expression of TGF alpha was also significantly greater in the gallbladders of patients with pancreaticobiliary maljunction than in the control gall-bladders, In conclusion, these results suggest that the increased TGF alpha expression induced by pancreaticobiliary maljunction promotes proliferation of the gall-bladder epithelium, which may lead to carcinogenesis.