Expression Of MMR Protein In Endometrial Cancer And Immune Characteristics Of MSI Endometrial Cancer

Objective:To explore the application of mismatch repair?MMR?proteins in clinical screening of Lynch syndrome and detection of microsatellite instability?MSI?endometrial cancer.To compare and analyze the differences of clinicopathological characteristics between endometrial cancer with different expressions of mismatch repair proteins.To express differences in the immune microenvironment between microsatellite unstable endometrial cancer and microsatellite stable?MSS?endometrial cancer.To discuss the meaning of mismatch repair proteins in clinical diagnosis and treatmentMethod:The clinical and pathological data of 404 patients with endometrial cancer who were treated in the gynecology department of the Affiliated Hospital of Qingdao University from September 2017 to September 2019 were collected,and the expression of mismatch repair protein?MLH1,MSH2,MSH6,PMS2?in endometrial cancer tissue was analyzed by immunohistochemistry among them.It showed that 97 patients with microsatellite unstable endometrial cancer?suspected Lynch syndrome?and 307 patients with microsatellite stable endometrial cancer.Analysis of age at onset,menstrual history,fertility history,body mass index?BMI?,comorbidities,family history,surgical-pathological stage?FIGO stage?,pathological grade,pathological type,lymph node metastasis and muscular layer infiltration depth between two groups was performed.30 patients were randomly selected from patients with microsatellite unstable endometrial cancer?suspected Lynch syndrome?and 10 patients were randomly selected from patients with microsatellite stable endometrial cancer.Immunohistochemical analysis of the expression of CD4,CD8,CD168,PD-1 and PD-L1 between the two groups was performed.After that,we analyzed the differences in immune microenvironment between the two groups of patients.Results:A total of 97?24.0%?patients with microsatellite unstable endometrial cancer?suspected Lynch syndrome?.Compared with endometrial cancer patients with missing mismatch repair protein expression and endometrium with normal mismatch repair protein expression,the expression of mismatch repair protein has no obvious correlation with clinicopathological characteristics.After compared the expressions of the four mismatch repair proteins,the following conclusions are drawn.Firstly,patients with loss of MLH1expression are more likely to develop type?endometrial cancer(P=4.26E^-11).Secondly,patients with loss of MSH2 expression show worse tumor differentiation?P=0.0481?.Lastly,patients with loss of MSH6 expression are more likely to have a family history related to Lynch syndrome,that is,the relatives of the patient are more likely to develop malignant tumors related to Lynch syndrome?P=0.0481?.The results of studies on the immune microenvironment show that there are differences in immune microenvironment between microsatellite unstable endometrial cancer and microsatellite stable endometrial cancer.It shows that patients with microsatellite unstable endometrial cancer showed more infiltration of CD8⁺T cells?P=0.3154?,less infiltration of macrophages?P=0.0496?and higher expression of PD-L1?P=0.0474?.Conclusion:The loss of mismatch repair protein expression is associated with clinicopathological features such as rare pathological types,family history of malignant tumors associated with Lynch syndrome,and poor tumor differentiation.Immunohistochemical detection of mismatch repair protein expression can be used to assist in the screening and diagnosis of Lynch syndrome.It is currently a more widely used method for screening patients with Lynch syndrome,which is helpful for targeted treatment and management.At the same time,it also screened out microsatellite unstable endometrial cancer patients.Endometrial cancer with missing expression of mismatch repair proteins have different immune microenvironments.Increased T lymphocyte infiltration,increased expression of PD-L1,and fewer macrophage infiltration show microsatellite unstable endometrium cancer may have stronger immunoreactivity,which means it may become a potential beneficiary of immunotherapy such as immune checkpoint inhibitors.