The Clinical Diagnostic Valuation Of Mismatch Repair (MMR) Protein In Lynch Syndrome-Associated Endometrial Carcinoma

ObjectiveTo retrospectively analyze and explore the clinical value of DNA mismatch repair gene(MMR)immunohistochemical results in screening Lynch syndrome associated endometrial carcinoma(LSAEC).To analyze the clinicopathological features of endometrial carcinoma between MMR protein expression deficiency and normal MMR protein expression.Methods From January 2016 to December 2018,patients with endometrial cancer who were treated by gynecological surgery in our hospital and confirmed by postoperative pathology with immunohistochemical staining containing MMR protein were selected.The clinical data of these patients were sorted out and divided into MMR protein expression deletion group and MMR protein expression normal group.Collecingt personal history and family history with Amsterdam II and Chinese standard of hereditary nonpolyposis colorectal cancer as the standard to classify the Lynch syndrome associated endometrial carcinoma and sporadic endometrial carcinoma.and evaluate the MMR protein expression immunohistochemical results of diagnostic value.At the same time,through the preoperative clinical data(including:age,BMI,with accompanying symptoms,family history and other complications such as hypertension,diabetes,etc.)and intraoperative pathological indicators(including:clinical stage,pathological type,depth of myometrial invasion,differentiation degree,diseased region,whether vascular invasion and lymph node metastasis,surgical procedure,etc.),to analyze the characteristics of endometrial carcinoma with MMR protein expression deficiency.ResultsAmong 154 cases of patients with endometrial cancer collected and selected,44 cases(28.57%)had MMR protein expression deficiency.The expression deficiency rates of MLH1,PMS2,MSH2 and MSH6 are 8.44%,19.48%,3.89%and 3.27%,respectively.The miss rate of MLH1 and PMS2 is 7.79%,and that of PMS2,MSH2 and MSH6 is 2.60%.1.Analysis on the risk factors of endometrial cancer:(1)the expression deletion rate of MMR protein in body mass index(BMI)≥24 and<24 was 17.39%and 31.48%,the difference is statistically significant(c~2=4.017,P=0.045).(2)the MMR protein expression deletion rate in patients with and without hypertension was 30.77%and 27.45%,the difference is not statistically significant(c~2=0.053,P=0.818).(3)the MMR protein expression deletion rate in patients with and without diabetes history are 26.67%and 29.03%,the difference of MMR protein expression deletion rate is not statistically significant(c~2=0.066,P=0.797).2.The pathological characteristics of endometrial cancer were analyzed:(1)the expression deletion rate of MMR protein in endometrial cancer is different in different age groups.The MMR protein deletion rate in patients≤50 years old and those aged>50 years old with is 48.00%and 19.23%,the difference is statistically significant(c~2=13.694,P=0.000),indicating that the MMR protein expression deletion group had earlier onset.(2)There is no significant differenceinMMRproteindeletionrateamongdifferentpathologicaltypes(c~2=0.000,P=1.000).(3)In the group of FIGO surgical and pathological stages,the MMR protein expression deletion rate are 27.74%,25.00%and 44.44%in stage I,II and III,the difference is not statistically significant(c~2=1.208,P=0.547).(4)In the pathological differentiation with high differentiation(G1),high-medium differentiation(G1/G2),medium differentiation(G2),medium-low differentiation(G2/G3)and low differentiation(G3),the MMR protein deletion rate are 12.68%,33.33%,38.89%,63.64%and 66.67%,The MMR protein expression group accounted for 87.32%,66.67%,66.11%,36.36%and 23.33%.With different degrees of differentiation,the difference of MMR protein expression deletion rate is statistically significant(c~2=21.985,P=0.000),and the MMR protein expression deletion group had lower degree of differentiation.(5)The MMR protein deletion rate in the<1/2 muscular layer and≥1/2 muscular layer are 25.37%and 50%,the difference is statistically significant(c~2=5.175,P=0.023).(6)The MMR protein expression deletion rate of endometrial cancer in the lower uterine segment and without the involvement of the lower uterine segment are52.94%and 25.55%,the difference is statistically significant(c~2=4.300,P=0.038).(7)In the cases with and without vascular invasion,the MMR protein expression deletion rate are48.00%and 19.23%,the difference is statistically significant(c~2=6.148,P=0.013).The MMR protein expression deletion group is more likely to have vascular invasion.(8)the MMR protein expression deletion rate in patients with and without lymphatic metastasis are 42.86%and 27.89%,the difference is not statistically significant(c~2=0.183,P=0.669).(9)MMR protein expression deletion rate are 25.00%,23.53%and 36.07%in the Ki67 expression negative,positive and strong positive,the difference is not statistically significant(c~2=2.756,P=0.252).3.According to the level ofⅡstandard or Chinese HNPCC family screening of 10 patients with endometrial carcinoma diagnosed with Lynch correlation,loss of MMR protein expression rate was 80%,the MMR normal protein expression rate is 20%,the difference is statistically significant(c~2=13.976,P=0.000),the MMR protein expression group are more likely susceptibility to Lynch syndrome associated endometrial carcinoma.Conclusion 1.The immunohistochemical method of MMR protein can be used as a preliminary screening method for LSAEC.2.Endometrial cancer with MMR protein expression deficiency has different clinical characteristics from endometrial cancer with normal MMR protein expression.The former has the following characteristics:lower BMI,earlier average age of onset,lower degree of differentiation,deep muscle infiltration,easy vascular infiltration,and easy occurrence in the lower uterine body.However,there are no significant correlation with pathologic type,pathological stage,lymph node metastasis and Ki index.