hMSH2 and GTBP expression in advanced stage epithelial ovarian cancer

Defects in DNA mismatch repair have been associated with both hereditary an d sporadic forms of human cancer. Most of the attention has been focused on the incidence and genetics of mismatch repair defects, while little is kno wn about the expression levels of the mismatch repair proteins and their si gnificance in cancer cell biology. In this study, both the expression level s of hMSH2 and GTBP proteins were investigated by Western blotting in 20 un treated epithelial ovarian cancers. For these analyses, a commercial anti-h MSH2 monoclonal antibody and a newly generated mouse monoclonal anti-GTBP a ntibody were used, hMSH2 and GTBP proteins were detected by Western blottin g in 19 out of 20 (95%) samples analysed and were found to be directly corr elated (r= +0.51, P = 0.025). hMSH2 expression was significantly higher in ovarian cancer cells originating from solid tumours than from ascites (H = 4.5, P = 0.033), whereas GTBP content did not significantly differ accordin g to the origin of cancer cells. No statistically significant differences w ere found in the distribution of hMSH2 and GTBP levels according to the age of the patients, grade of differentiation, histotype and extent of surgica l debulking. The amount of hMSH2 protein was demonstrated to be significant ly lower in stage IV than in stage III patients (H = 7.35, P = 0.007). More over, significantly lower hMSH2 levels were observed in non-responding pati ents compared to patients who achieved complete or partial response to cisp latin-based chemotherapy (H = 4.88, P = 0.027). Conversely, GTBP levels wer e not distributed differently according to stage of disease and chemotherap y response. Our study suggests a possible involvement of hMSH2 in ovarian c ancer cell biology and susceptibility to chemotherapy. The possible biologi cal and/or clinical role of GTBP expression in ovarian cancer patients rema ins to be elucidated.