MLH1 Mismatch Repair Gene Product is Associated with Apoptotic Potential of Urothelial Bladder Carcinomas

Abstract

Background: Mismatch repair genes are possibly involved in the tumorigenesis and/or progression of bladder cancer, as has been reported in colorectal and other cancers. Materials and Methods: The protein expression of one of these genes (MLH1) was examined in 121 patients with urothelial carcinoma (UC) of the bladder by an immunohistochemical technique. Results: Reduced expression of MLH1 protein was detected in 56 cases (46%) and was significantly more frequent in pT₂ UCs (p=0.039). In superficial disease (T_a-T₁ tumors), preserved expression of the MLH1 protein was detected in tumors with high proliferation indices, as evidenced by Ki-67 immunostaining (p=0.046). Interestingly, low MLH1 levels were positively-associated with the possibly low apoptotic potential of the tumor cells, as evidenced by decreased caspase-3 (CPP32) immunoreactivity (p=0.050). Conclusion: A significant proportion of UCs revealed low positivity percentages for MLH1 expression, probably reflecting MLH1 gene dysfunction in the respective cases. Preserved MLH1 expression was associated with highly proliferating cells, which are more likely to need DNA repair systems. A reduced expression of MLH1 may exert an adverse influence on the apoptotic potential of cancer cells.