The Expression And Clinicopathological Significance Of Mismatch Repair Proteins (MLH1,MSH2,MSH6 And PMS2) In Endometrial Carcinomas

Objective:To analyze the expression and clinicopathological significance of mismatch repair protein(MLH1,MSH2,MSH6 and PMS2)deficiency in the endometrial carcinoma tissues,and accumulate of MMR protein abnormal expression data in China,in order to further explore the molecular pathogenesis of endometrial carcinoma.Methods:Three handred and ninteencases of endometrial cancer patients tissue(endometrial cancer group)as the experiment group,20 cases of atypical hyperplasia of endometrium tissues(Hyperplasia group)and 20 cases of normal endometrium tissues(the normal group,which got from hysteromyomectomy)as the comparison group treated in Chinese PLA General Hospital from Jan.2005 to Dec.2016 were enrolled.The expression of MMR proteins(MLH1,MSH2,MSH6 and PMS2)were assessed by immunohistochemistry(IHC).The weight and height of the patients were recorded to calculate the body mass index(BMI=weight(kg)/height2(m));The methylation status of MLH1 was detected by MLPA.Then use SPSS 21.0 to analyze the expression and clinical significance of MMRs by adopting ?2 test and Fisherman exact probability test.When the p<0.05.the difference has statistically significant.Results:General condition:319 patients were enrolled,and the 95%CI age was[54.96 +10.27].266 patients aged 45 years and above,accounting for the vast majority of patients,95%CI BMI:[25.84 + 4.19].319 Cases of tumor location:186 cases were in the fundus,81 cases in uterus body,52 cases in lower uterine segment.243 cases were in FIGO I stage,accounting for 76.18%,43 cases in stage ?,accounting for 13.48%,30 cases in stage ?,accounting for 9.40%,and 3 cases in stage IV,accounting for only 0.94%.Pathological type:endometrioid carcinoma in 294 cases,accounting for 92.25%of the total;clear cell carcinoma in 18 cases,up to 5.54%,while serous carcinoma in 7 cases,2.21%.In the endometrioid EC,there were 185 cases with high differentiation,84 cases with moderate differentiation,and 25 cases with low differentiation,accounting for 62.93%,28.57%and 8.50%,respectively.There were 221 cases(69.28%)with lymphoid-infiltration and 98 cases without lymph invasion.MLH1 lost expression in 46 cases,accounting for 14.42%of the total number of EC patients.The lost expressions of MSH6 and MSH2 were 6.58%and 6.27%,respectively.While 91 cases of PMS2 were absent,accounting for 28.53%.For FIGO staging,with staging increase,the expression rate was significantly decreased in mismatch repair genes MSH2 and MSH6,and the loss rate of expression between different FIGO stages(I-IV)had significant difference,pvalues were 0.048 and 0.005,respectively.The rate of exprerssion loss of PMS2 was significantly lower in endometrial cancer than that in other pathological types(p=0.0002).Except that the positive rate of PMS2 in well differentiated endometrioid carcinoma and middle differentiation has significant difference(p=0.0346),there was no statistically significant between other proteins and cancer differentiation.There was no significant correlation between the expression of MMR protein with BMI?tumorlocationor lymphatic infiltration in tumors.For MLH1 immunohistochemical loss of expression specimens,the number of methylation cases was 7 cases,accounting for 25.93%.Conclusion:1.EC patients with age older than 45 years are account for the majority(83.39%).The main pathological type is endometrioid carcinoma,and most of them are in stage FIGO-I.2.There was no statistical difference between the expression of mismatch repair gene in different tumor site or tumor interstitial lymphocyte infiltration,and there was no correlation with BMI.3.The expression of MSH2 and MSH6mostly decreased in FIGO-II stage.4.The expression rate of PMS2 in endometrioid carcinoma was significantly higher than that in other pathological types,and the expression rate of PMS2 in well differentiated endometrioid carcinoma was significantly higher than that in moderately differentiated carcinoma.5.Hypermethylation of promoter was found in about 1/4 patients with immunohistochemical loss of MLH1 expression.6.Early detection of Lynch's syndrome may be performed by immunohistochemistry combined with clinical data of patients.