The Expression Of PD-1/PD-L1 In Endometrial Carcinoma And Its Relationship With Clinical Therapeutic Effect Of Monoclonal Antibodies

Endometrial carcinoma is a kind of tumor with great difference and heterogeneity in biological,molecular and pathological development.At present,with the development of medical technology,the depth of human research on malignant tumors continues to deepen.Immunotherapy represented by PD-1 and PD-L1 has gradually been widely used in the treatment of recurrent,metastatic and refractory gynecological malignant tumors.At present,immunotherapy for endometrial cancer patients is in the exploratory stage.This study is a clinical study and analysis of the efficacy and late survival of immunotherapy with PD-1/PD-L1 in endometrial carcinoma.Methods: 50 patients with advanced or recurrent endometrial cancer(EC group)and 50 patients with endometrial benign lesions confirmed by pathology(benign group)were selected from the second tumor hospital of Heilongjiang Province(Beidahuang Group General Hospital)from January 2018 to January 2021.EC group was treated with PD-1/PD-L1 monoclonal antibodies for 6-12 months after the completion of the standard endometrial cancer treatment regimen.Immunohistochemical staining method was used for detecting the expression of PD-1,PD-L1 and EGFR in endometrial cancer tissues.Analysis: the expression of PD-1,PD-L1 and EGFR in endometrial carcinoma patients and benign group were analyzed.Then combined with the expression of PD-1/PD-L1,patients in EC group were divided into two groups: PD-1/PD-L1 positive group and PD-1/PDL1 negative group.The histological and pathological grades of patients in the two groups were compared and analyzed,and the relationship between PD-1 positive or PD-L1 positive expression and prognostic risk factors was analyzed.After treatment with PD-1/PD-L1 monoclonal antibody,the efficacy,adverse reactions and survival time of patients with positive PD-1/PD-L1 expression and patients with negative PD-1 and PD-L1 were compared and analyzed.Results:1.Expression of PD-1,PD-L1 and EGFR in endometrial carcinomaThe expression of PD-1 and PD-L1 in endometrial carcinoma and enign group after treatment: the positive expression rate of PD-1 in benign group was 4% In EC group,the positive rate of PD-1 staining was 66%(P< 0.001).The positive expression rate of PD-L1 in benign group was 34%;In EC group,the positive rate of PD-L1 staining was 52%(P>0.05).In addition,22% of the samples in benign group showed positive EGFR staining,and 76% of the samples in EC group showed positive EGFR staining(P < 0.05).The expression of PD-1 and EGFR in benign group and EC group was significantly different.2.Relationship between pd-1/pd-l1 expression and EC disease stageIn the PD-1/PD-L1 positive group,there were 35 cases,6 cases in grade I,accounting for 17.14%,19 cases in grade II,accounting for 54.28%,and10 cases in grade III,accounting for 28.57%.There were 15 cases in PD-1/PD-L1 negative group,8 cases in grade I,accounting for 53.33%,2 cases in grade II,accounting for 13.33%,and 5 cases in grade III,accounting for33.33%.B.According to the pathological stage,the incidence of EC disease: in the PD-1/PD-L1 positive group,there were 35 cases,13 cases in grade II,accounting for 37.14%,and 22 cases in grade III and IV,accounting for 62.86%;There were 15 cases in PD-1/PD-L1 negative group,9 cases in grade II,accounting for 60.00%,and 6 cases in grade III and IV,accounting for 40.00%.There is significant difference between two groups(P < 0.05).3.Relationship between PD-1,PD-L1 expression and prognostic risk factors in EC patientsIn 50 EC patients,33 cases(65.0%)had PD-1 positive expression in endometrial sections.High risk grade,depth of invasion and maximum diameter of tumor were correlated(P < 0.05).While age parameter,lymphatic space invasion and cervical mucosal gland invasion had no correlation characteristics(P > 0.05).The positive expression of PD-L1 in26 cases(52.4%)was significantly correlated with histological grade(P <0.05).4.Relationship between the theraputic effect of EC patients after treatment and the expression of PD-1/PD-L1After receiving the treatment with immune checkpoint inhibitors,the ratio of patients with complete remission plus partial remission in the PD-1/PD-L1 positive group was 88.5%.In PD-1/PD-L1 negative group,the ratio of patients with complete remission plus partial remission was 33.4%(P < 0.05).5.Relationship between the incidence of adverse reactions and PD-1/PD-L1 expression in EC patients after treatmentAmong EC patients,in PD-1/PD-L1 positive group,the incidence of anorexia,malignancy,vomiting,leucopenia,neutropenia,febrile neutropenia and anemia was significantly lower than that in PD-1/PD-L1 negative group(P < 0.05).There was no significant difference in the incidence of other adverse reactions between the two groups(P < 0.05).Most of the adverse reactions occurred in EC patients treated with PD-1and PD-L1 monoclonal antibodies were mild.The incidence of adverse reactions above grade III was less,and there were no grade IV and V adverse reactions.Through standardized follow-up,early detection and early treatment,and the vast majority of related adverse reactions can be improved through drug withdrawal,hormone and other treatment.The total incidence of adverse reactions in PD-1/PD-L1 positive group was 25.71%,mainly gastrointestinal symptoms.And that in PD-1/PD-L1 negative group was 46.67%.There was statistical significance between the two groups(P< 0.05).6.Relationship between survival and PD-1/PD-L1 expression in EC patients after treatmentFifty patients in PD-1/PD-L1 positive group survived for 1 and 2 years,with a survival rate of 100.0%.Fourteen patients in PD-1/PD-L1 negative group survived for 1 year,accounting for 93.0%;10 patients survived for2 years,accounting for 67.0%.Comparison of 1-year and 2-year survival rate between the two groups are significant difference(P < 0.05).Conclusion:1.The expression of PD-1 and EGFR in endometrial cancer tissue of endometrial cancer patients is higher than that of benign group.2.The expression of PD-1/PD-L1 is closely related to the staging and prognostic risk factors of EC patients.3.EC patients with PD-1/PD-L1 positive expression have high treatment efficiency,low adverse reactions and prolonged survival.In conclusion,this study confirmed that the therapeutic effect of PD-1or PD-L1 blockade in PD-1/PD-L1 positive patients was better than that in PD-1/PD-L1 negative EC patients.The expression of PD-1 and PD-L1 is a risk factor for the prognosis of EC patients.It can predict the depth of myometrial invasion and the current degree of cancer differentiation.The use of PD-1 and PD-L1 can effectively evaluate and guide the early diagnosis and late treatment effect of patients.