Abstract

Objective: To explore the expression and clinical significance of mismatch repair (MMR) protein and MLH1 promoter methylation testing in endometrial cancer (EC) . Methods: A total of 420 cases with EC diagnosed by the surgical pathology examination from the Department of Pathology of PLA General Hospital, MLH1, MSH2, MSH6 and PMS2 protein in EC were detected by immunohistochemistry and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) testing. Results: (1) Of the 420 tumor cases, the total expression loss rate of MMR protein was 34.5% (145/420) , the expression loss rates of MLH1, MSH2, MSH6 and PMS2 protein were respectively 17.1% (72/420) , 8.1% (34/420) , 7.4% (31/420) , 26.2% (110/420) and loss rates of MLH1 and PMS2, MSH2 and MSH6 were16.7% (70/420) , 6.2% (26/420). When there was a loss of MMR protein expression, any one or more protein expression deletions in MLH1, PMS2, MSH2 and MSH6, it could be Lynch syndrome related endometrial carcinoma (LS-EC). The expression loss rate of MMR protein in the poorly differentiated endometrioid adenocarcinoma was higher than that in the well differentiated endometrioid adenocarcinoma (P<0.05). (2) The expression loss rate of MMR and PMS2 protein had statistically significant between the endometrioid adenocarcinoma and non-endometrioid adenocarcinoma (P<0.01). The expression loss rate of MSH2 protein had statistically significant in the stage Ⅲ (P<0.01). Moreover, there were also significant differences in depth of myometrial invasion and lymph node metastasis between the expression loss rate of MMR protein (P<0.05). (3) The expression loss rate of MLH1 protein was 72 cases and 57 cases had MLH1 promoter methylation testing (excluding those who were not qualified for DNA testing). The positive rate was 47.4% (27/57). Therefore, these patients were sporadic endometrial cancer, not non-LS-EC. Conclusions: MMR protein may be play an important role in the development of endometrial cancer and be indicated poor prognosis. Immunohistochemical staining and MLH1 promoter methylation detection may be play an important role in the screening of the LS-EC.

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