Expression And Clinical Significance Of MSI And PD-L1 In HER2-positive Gastric Cancer

Objective:Patients with HER2-positive metastatic/unresectable gastric cancer have a poor prognosis.Trastuzumab combined with chemotherapy is currently the standard treatment modality,but the combined survival benefit is limited.Immunotherapy is considered to be the most promising treatment in tumor therapy,but its application in gastric cancer is still not ideal,and there is a lack of ideal biomarkers for screening effective populations.The expression levels of microsatellite instability(MSI)and programmed death ligand 1(PDL1)have been shown to be closely related to the efficacy of immunotherapy in multiple tumor types,however,there are few studies on the correlation between HER2 status,MSI status and PD-L1 expression in gastric cancer patients.This study aimed to verify the consistency of next-generation sequencing(NGS)and immunohistochemistry(IHC)in the assessment of HER2 status,analyze the relationship between MSI status,PD-L1 expression and clinicopathological characteristics,and explore the prognostic factors of patients with HER2-positive gastric cancer.Methods:A total of 92 patients who underwent gastric cancer surgery at the Affiliated Hospital of Qingdao University and whose postoperative tissue specimen was IHC HER2 3+ were collected.Detection of HER2 gene amplification and MSI status in cancer tissues by NGS detection technology,PD-L1 expression in cancer tissues by PD-L1 IHC 22C3 pharm Dx(Dako),with combined positive score(CPS)and tumor positive score(TPS)calculation.Results:1.In this study,there were 92 cases of gastric cancer patients with IHC HER2 3+,NGS detection technology found 84 patients with HER2 gene amplification,and 8(8.7%)patients did not find HER2 gene amplification.The results of IHC and NGS detection technology The agreement is 91.3%.2.Of the 92 patients with HER2-positive(IHC HER2 3+)gastric cancer,90 patients(97.8%)with microsatellite stabilization(MSS)and2 patients(2.2%)with microsatellite instability high(MSI-H).The 84 patients with HER2 gene amplification were all MSS and no MSI-H patients.3.CPS scoring standard results,92 cases of HER2-positive(IHC HER2 3+)patients had a PD-L1 positive rate of 89%,of which 81.5% were patients with PD-L1 CPS ?5,and 55% were patients with PD-L1 CPS?10,there is no correlation between PD-L1 expression and clinicopathological characteristics.4.The results of TPS scoring standard showed that the PD-L1 positive rate among the 92 HER2-positive patients was 24%,and there was no correlation between PD-L1 expression and clinicopathological characteristics in patients,without patients of PD-L1 TPS ?50%.5.COX regression analysis shows that poor tumor differentiation and late postoperative staging are adverse factors affecting the prognosis of HER2-positive gastric cancer patients,and post-operative staging is an independent factor affecting the prognosis of patients.Regardless of whether TPS or CPS scoring standards are used,in HER2-positive gastric cancer tissues,the expression of PD-L1 in the middle of the patients has nothing to do with the overall survival after operation.Conclusion:The gastric cancer tissues with HER2-positive immunohistochemical detection confirmed by NGS detection technology that the agreement rate was 91.3%.There may be a mutually exclusive relationship between HER2 gene amplification and MSI-H in gastric cancer tissues.The HER2-positive gastric cancer has a higher PD-L1 positive rate under the CPS scoring standard than the TPS scoring standard,but has nothing to do with overall survival after surgery.Poorly differentiated tumors and late stages are poor prognostic factors for HER2-positive gastric cancer.