Screening Lynch-syndrome Associated Endometrial Cancer And Its Clinicopathological Features

Objective: The aim of this study is to screen Lynch syndrome in endometrial cancer patients and to compare clinicopathological features of patients with Lynch syndrome associated,sporadic and Lynch-like syndrome associated endometrial cancer in our center.Meanwhile,analyze the missed diagnosis rate and significance of the history screening criteria.Methods: From August 2016 to October 2017,372 cases of Tianjin Central Hospital of Gynecology Obstetrics were selected as subjects of the study.372 patients underwent standard endometrial cancer surgeries were diagnosed as endometrial cancer by postoperative pathology.The endometrial tissues collected were formalin fixed paraffin embedded tissues,and the immunohistochemistry of MMR proteins(MLH1,MSH2,MSH6,PMS2)were applied.MLH1 methylation and genetic testing were offered to part of the patients.The clinicopathological data of all patients were collected.Results: 1)Experimental Result: Of the 372 endometrial cancers,106 were MMR protein deficient(MMR-d).64 patients with MLH1 methylation accounted for 90.1% of all MLH1/PMS2 deficient patients.A total of 42 patients of MLH1/PMS2 protein deficient with MLH1 methylation negative or MSH2/MSH6 protein deficient were selected for next generation sequencing.20 had germline mutations in MMR genes(including EPCAM)and were diagnosed with Lynch Syndrome(LS group).22 with no germline mutations in MMR genes were named Lynch-like syndrome(LL group).The remaining 330 cases were sporadic endometrial cancers(sporadic group).2)Clinicopathological features of LS group and sporadic group: 15 cases(75.0%)in LS group were under 50 years old and 5 cases(25.0%)were not.The LS patients were younger than sporadic patients(p=0.010).The lower uterine segment of 14 cases(70.0%)in LS group were infiltrated.Infiltration rate of lower uterine segment in LS patients was higher than that in sporadic patients(p=0.011).12 cases(75.0%)in LS group had Lynch syndrome associated cancers in personal history/family history.The percentage in LS patients was higher than that in sporadic patients(p<0.001)and that in LL patients(p=0.012).BMI,clinical stage,histopathologic type,tissue differentiation of type I endometrioid adenocarcinoma,the depth of myometrial invasion,the positive rate of lymphovascular space invasion and positive rate of pelvic lymph nodes were not significantly different between LS group and sporadic group(p>0.017).3)There is no significant differences in clinicopathological features between LL group and LS group or sporadic group(p>0.017).4)Analysis of history screening criteria: Rate of missed diagnosis of Amsterdam II criteria and the Revised Bethesda criteria was 85.0% and 80.0%,respectively.Conclusions:1)MMR protein deficiency is common in endometrial cancer(28.5%).MLH1/PMS2 protein deficiency accounts for the highest percentage(70.0%).It is important to apply MLH1 methylation test in these patients to rule out sporadic endometrial cancer.2)MLH1 methylation accounts for about nine-tenths(90.1%)of all MLH1/PMS2 protein deficiency.3)Lynch syndrome associated endometrial cancer,as opposed to sporadic endometrial cancer,has clinicopathological features included young age,frequent invasion to the lower uterine segment and high percentage of Lynch syndrome associated cancers in personal history/family history.However,there was no significant differences between the two groups in BMI,clinical stage,histopathologic type,tissue differentiation of type I endometrioid adenocarcinoma,the depth of myometrial invasion,the positive rate of lymphovascular space invasion and positive rate of pelvic lymph nodes.4)There were no significant differences in clinicopathological characters between Lynch-like syndrome associated endometrial cancer and sporadic endometrial cancer.5)The use of the Amsterdam II criteria and the Revised Bethesda criteria in endometrial cancer has a high rate of missed diagnoses and a low positive predictive value.History screening is of limited value in the diagnosis of Lynch Syndrome.6)According to the regional situation,selective use of universal screening or combination of clinicopathological features for Lynch Syndrome screening has a good prospect in China.