The Correlation Between Phosphorylation Of Gsk-3β And Expression Of Pms2 In Epithelial Ovarian Carcinoma

Objective: The purpose of the study is to elucidate the correlation between glycogen synthase kinase 3 beta(GSK-3β) phosphorylation and Postmeiotic segregation increased2(PMS2) expression and their correlation with clinicopathologic parameters.Methods:The immunohistochemical activity of GSK-3β, pGSK-3βand PMS2 in 67 samples, including 10 benign cases, 9 borderline cases, 48 malignant cases and 11 normal cases, was defined using immunohistochemistry double staining. Analysis the correlation between pGSK-3βand PMS2.The mRNA levels of GSK-3β, PMS2 andβ-catenin(substrate of GSK-3β) were also determined in 15 normal specimens and 60 primary epithelial ovarian tumor specimens including 11 benign cases, 8 borderline cases, 41 malignant cases using Real-time quantitative PCR.Results:Immunohistochemistry results demonstrated there was a markedly elevated activity of GSK-3βin malignant tumors, compared with normal tissue(p=0.005) and benign tumors(p=0.003). pGSK-3βexpression in malignant tumors was much more significant than that normal tissue(p=0.007) and in benign tumors(p=0.014), while a significantly lower PMS2 activity was observed in malignant tumors than that in normal specimens (P<0.001). Correlation analysis revealed that the expression of pGSK-3βis negatively correlated with that of PMS2 in malignant tumors(P<0.001). The expression of PMS2 in poorly-moderately differentiated malignant tumors was lower compared with well differentiated malignant tumors(p=0.027).Real-time quantitative PCR results showed that the levels of mRNA of GSK-3β, PMS2 andβ-catenin in malignant tumors were significantly higher than those in benign tissues(p=0.009,p=0.048,p=0.017). Pearson correlation analysis revealed that GSK-3βmRNA levels in ovarian epithelial cancer were positively correlated with PMS2 andβ-catenin mRNA levels(r=0.537,P<0.01;r=0.639, P<0.01 respectively). The levels of mRNA ofβ-catenin in well differentiated malignant tumors and stagingⅠ-Ⅱwere higher compared with poorly-moderately differentiated malignant tumors(p=0.036) and stagingⅢ-Ⅳ(p=0.029).Conclusions: The elevated expression of GSK-3βand its substrateβ-catenin in ovarian cancer suggest that their potential role in ovarian tumor genesis. The different PMS2 expression in ovarian cancer showed its significantly relationship with the origin of tumor. Given the observed correlation between pGSK-3βand PMS2 in this study, we think it is plausible that GSK-3βcan contribute to ovarian tumor genesis by phosphorylating PMS2.