EGFR,KRAS Gene Mutation And PD-L1 Expression In Thymic Epithelial Tumors And Their Clinical Significance

Background and purpose:Thymic epithelial tumors(TETs)are rare tumors produced by thymic epithelial cells,mostly in the anterior superior mediastinum.They are mainly divided into thymoma and thymic carcinoma(TC).They are more common in the middle-aged and elderly people.Significant differences.It is generally believed that complete surgical resection is the preferred treatment for TETs and is the most important method for patients to achieve long-term survival.For unresectable local advanced tumors or stage IV thymic tumors,the current mainstream treatment plan is radiotherapy + chemotherapy.However,the patient’s objective response rate is less than 50%,and the toxic side effects of radiotherapy and chemotherapy also make patients miserable.Therefore,patients with TETs urgently need new treatments to improve their prognosis and quality of life.In recent years,molecular targeted therapy and immunotherapy have become a hot topic in the treatment of cancer.Among them,EGFR and KRAS gene mutations and PD-L1 positive expression have been confirmed in different types of tumors,and most of them have poor prognosis with these tumors.Relevance,related drug treatment also achieved objective progress.However,the current studies on the mutations of EGFR and KRAS genes in TETs and the positive expression of PD-L1 in TETS have lagged behind.The purpose of this study was to observe the mutations and expression of EGFR and KRAS genes and PD-L1 in thymic epithelial tumors,and to explore the effects of PD-L1 on the prognosis of TETs.Methods:1.Collect 38 specimens of thymoma or thymus carcinoma diagnosed by pathological examination at the Department of Thoracic Surgery,Affiliated Hospital of Qingdao University from January 2015 to June 2017.Direct sequencing was used to detect EGFR(exon)in thymic epithelial tumors.18,19,20,21)gene and KRAS(exon 2,3)gene mutations,and analysis of EGFR and KRAS gene mutations in patients with clinical pathological parameters(age,gender,whether combined with muscle weakness symptoms,WHO points Type,Masaoka-Koga stage,whether the tumor is completely removed)whether there is a correlation.2.A total of 90 patients with thymoma or thymus cancer confirmed by pathological diagnosis at the Department of Thoracic Surgery,Affiliated Hospital of Qingdao University from January 2005 to December 2007 were collected.All patients were well-prepared.All pathological specimens were obtained from the Affiliated Hospital of Qingdao University.Pathologists were confirmed by sections stained with HE and immunohistochemical staining.After specimens were obtained,they were treated with 10% buffered formalin and embedded in paraffin.Immunohistochemistry was used to analyze the expression of PD-L1 in thymic epithelial tumors.The correlation between PD-L1 expression and clinicopathological parameters(age,gender,presence of muscle weakness,WHO classification,Masaoka-Koga staging,and complete tumor resection)was analyzed.Through follow-up of patients,the relationship between the expression of PD-L1 and the prognosis of TET patients was analyzed.The follow-up time was from 6 to 20 months.The overall survival(OS)was the survival time from the date of diagnosis to death or at the final follow-up.Statistical methods: The chi-square test was used and the KruskalWallis rank-sum test was used to assess the correlation between gene mutations and protein expression and clinicopathological parameters.Through follow-up of patient outcomes,overall survival was described using the Kaplan-Meier univariate survival analysis and Logrank test was used to assess differences in survival curves.Cox multivariate regression analysis model was used to analyze the independent prognostic factors of thymic epithelial tumors.The above data processing is implemented by SPPS 24.0.P values ??less than 0.05 were considered statistically significant.Results:1.In 38 cases of thymic epithelial tumor tissue,two cases of EGFR gene mutations were detected.EGFR mutations were the L858 R mutation in exon 21 of type B3 thymoma and the G863 D mutation in exon 21 of thymic carcinoma.No KRAS gene was detected.mutation.2.Twenty-six(28.9%)cases of PD-L1 were highly expressed in 90 cases of thymic epithelial tumors.The positive rate of thymoma(46.2%)was significantly higher than that of thymoma(21.9%).More importantly,the high expression of PD-L1 was significantly associated with TET high stage(III + IV stage: P <0.05)and high grade subtype(B3 +thymic carcinoma: P <0.05).In addition,after Fisher’s exact test,the correlation between PD-L1 and whether the tumor was completely resected was also statistically significant.By univariate survival analysis,PD-L1 positive expression,WHO high-grade subtype,Masaoka high-grade and incomplete resection of tumors were significantly associated with poor 10-year survival rate of patients with TETs(P<0.05).After COX multifactorial It was found that high PD-L1 expression,WHO high-grade subtype,and Masaoka high-grade were independent predictors of prognosis in patients with thymic epithelial tumors(P<0.05).Conclusion:1.The mutation rate of EGFR and KRAS genes in thymic epithelial tumors is low,but it can be highly expressed in tumor cells.EGFR or KRAS genes should still be further studied in patients with sub-optimal thymic epithelial tumors,so as to be able to obtain Patients benefit from individualized treatment.2.PD-L1 is differentially expressed in different stages and grades of thymic epithelial tumors,and has different effects on the prognosis of patients with TETs.Therefore,PD-L1 positive expression plays an important role in the development of thymic epithelial tumors.The data from this study demonstrate that high PD-L1 expression can be used as a predictor of prognosis in patients with thymic epithelial tumors.