The Expression And Clinical Significance Of Mismatch Repair Protein In Lynch Syndrome-associated Endometrial Carcinoma

Objective: 1.To screen out probable LS-associated EC by detecting the expression of mismatch repair(MMR)proteins and evaluate the characteristics of probable LS-associated EC in China.2.To learn about MLH1 promoter methylation status among cases with MLH1/PMS2 loss.Methods: 1.Four types of MMR proteins,MSH2,MSH6,MLH1,and PMS2,were detected using immunohistochemistry(IHC)on 443 cases of unselected patients with EC.2.MLH1 promoter methylation analysis was performed on cases demonstrated loss of MLH1/PMS2 immunohistochemical expression.Results: 1.Among the 443 cases of patients,115 cases of patients were MMR protein deficient and were defined as probable LS cases.2.The probable LS cohort was prone to the absence of obesity and was diagnosed with poorly differentiated tumor compared with the sporadic cohort(p =0.04,p = 0.012 respectively).However,differences in the age of diagnosis,clinical features,family history,and pathological variables were not significant between the probable LS and sporadic cohorts(p >0.05).3.A higher tumor grade was more common in the MSH6 and PMS2 deficient groups(p = 0.012).4.Compared to sporadic EC,BMI <28 Kg/ m2(p =0.000),positive family history of cancer(p =0.037)and the presence of previous or synchronous cancers were more common in the MSH2/MSH6 deficient group,and a higher tumor grade was more common in the MSH6 and PMS2 deficient groups(p =0.000 and p =0.015 respectively).5.Hypermethylation testing was performed on 48 cases with MLH1/PMS2 loss.Because of lacking of tumor specimens and specimen quality,satisfactory results were obtained in 14 cases and all showed MLH1 promoter hypermethylation.Conclusion: 1.Probable LS cases universally screened by IHC accounted for 26% in EC in Shanxi province.2.Personal history of cancers may be valuable in the diagnosis of LS-associated EC.3.The absence of obesity,a high grade tumor are more common in probable LS cases.4.Hypermethylation of the MLH1 gene promoter is common in the cases demonstrated loss of MLH1/PMS2 immunohistochemical expression.