Clinicopathological Characteristics Of Endometrial Cancer Molecular Risk Classifier And Relationship With Prognosis

Objective:To study the sub-classification method of TCGA molecular classification of Endometrial Cancer:the relationship between the proactive molecular risk classifier for endometrial carcinoma(ProMisE)and the clinicopathological characteristics and prognosis of patients with endometrial cancer To explore whether it can be used as a clinically applicable alternative molecular classifier to provide reference and predictive significance for the selection of treatment strategies and judge prognosis for patients with endometrial cancer.Methods:The clinicopathological data and follow-up data of 331patients with endometrial cancer admitted to the Affiliated Tumor Hospital of Guangxi Medical University from August 2015 to December2019 were selected,and the MMR gene in the patient’s endometrial cancer tissue was detected by immunohistochemistry(Including MLH1,MLI-L2,PMS2 and MLH6)expression loss and P53immunohistochemistry,perform ProMisE,and analyze it with the patient’s age of onset,ethnicity,height,weight,whether menopause,whether it is combined with medical diseases,FIGO staging,FIGO The relationship between grade,histological type,involvement of the lower uterus,lymph node metastasis,lymphatic vascular tumor thrombus infiltration,tumor size,mismatch repair gene expression and P53expression.Use Kaplan-Meier to draw survival curve,perform log-rank test(Log-rank-test)for difference analysis,and use Cox regression model to analyze factors affecting overall survival(OS)of patientsResult:1.Among the 331 patients with endometrial cancer,there were 272 cases(82.18%)in MSS status,59 cases(17.82%)in MMR-D status,33 cases(9.97%)in MSI-H status,and 92 cases in P53-abn Cases(27.79%),180 cases(54.38%)of P53-wt.The deletion rate of the four mismatch repair genes in endometrial cancer:23 cases(6.95%)of MLH1protein deletion,17 cases(5.14%)of MLH2 protein deletion,17 cases(5.14%)of MLH6 protein deletion,and PMS2 protein deletion 39 cases(11.78%).2.The lack of MMR protein in endometrial cancer and the presence of MSI-H expression are related to the tissue type and the presence of lymphatic vessel tumor thrombi(P<0.05).Loss of MLH1protein expression was related to age and the presence of lymphatic vessel tumor thrombi(P<0.05).Loss of MLH2 protein expression was related to age,ethnicity,tissue type,tumor size,and involvement of the lower uterus(P<0.005).Loss of MLH6 protein expression is related to tissue type(P<0.005).Loss of PMS2 protein expression is related to tissue type,FIGO grade,lymphatic vessel tumor thrombus and lymph node metastasis(P<0.005).3.The relationship between molecular classification of endometrial cancer and clinicopathological characteristics:MMR-D type is related to tissue type,FIGO grade,tumor size,involvement of the lower part of the uterus,presence of lymphatic vascular tumor thrombi,and lymph node metastasis(P<0.05).P53-wt type is related to FIGO classification(P<0.05).4.Among the 331 patients with endometrial cancer,44 died.According to Kaplan-Meier analysis,compared with the MSS group,the survival curves of the patients in the MMR-D group of endometrial cancer have statistically significant differences between the two groups(X~2=3.932,P=0.047).Compared with the P53-abn group,the survival curves of the patients in the MMR-D group of endometrial cancer were statistically significant(X~2=8.449,P=0.004).Compared with the P53-wt group of patients with endometrial cancer,the MMR-D group had no significant difference in survival curves between the two groups(X~2=1.172,P=0.279).Compared with the P53-abn group of patients with endometrial cancer,the difference in survival curves between the two groups was statistically significant(X~2=9.018,P=0.003).5.The clinical pathological factors and the OS of endometrial cancer patients were analyzed by COX.Single-factor COX regression analysis found P53-abn(HR=12.182,P<0.000),age(HR=4.409,P=0.036),tissue type(HR=16.041,P<0.000),FIGO classification(HR=19.188,P<0.000),FIGO staging(HR=23.552,P<0.000),depth of invasion(HR=4.614,P=0.032),involvement of the lower uterus(HR=4.577,P=0.032),lymph node metastasis(HR=15.307,P<0.000),surgical method(HR=11.811,P=0.001)are related to OS in patients with endometrial cancer.Further analysis of multivariate COX adjustment showed that FIGO staging(HR=4.127,P=0.042),P53-abn(HR=6.131,P=0.012),and surgical method(HR=4.748,P=0.029)are the factors that affect the patient’s OS Independent risk factors.Conclusion:1.MMR-D type is closely related to the tissue type of endometrial cancer,FIGO grade,tumor size,involvement of the lower part of the uterus,the presence of lymphatic vessel tumor thrombi and lymph node metastasis.2.ProMisE molecular classification can be used as a clinically applicable molecular classifier to provide reference and predictive significance for the selection of treatment strategies and prognosis for patients with endometrial cancer.3.The OS of patients with endometrial cancer is related to P53-abn type,age,tissue type,FIGO grade,FIGO stage,depth of tumor invasion,tumor involvement in the lower part of the uterus,presence of lymph node metastasis,and laparoscopic surgery.Among them,FIGO staging,P53-abn type,and laparoscopic surgery are independent risk factors that affect patients’OS.4.The specific clinical application of ProMisE molecular typing still needs further research in multi-center and large samples.