Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer

Diagnostic Pathology

Dongliang Wang¹  Yinkui Wang²  Ziyu Li²  Aiwen Wu²  Linxin Zhou³  Dongmei Lin³  Zhongwu Li³  Li Zhang³  Yiqiang Liu⁴ 

[1] ChosenMed, Beijing Economic-Technological Development Area, 100176, Beijing, People’s Republic of China;Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital, No.52 Fucheng Road Haidian District, 100142, Beijing, People’s Republic of China;Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital, No.52 Fucheng Road Haidian District, 100142, Beijing, People’s Republic of China;Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital, No.52 Fucheng Road Haidian District, 100142, Beijing, People’s Republic of China;Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital, No.52 Fucheng Road Haidian District, 100142, Beijing, People’s Republic of China;

关键词: Gastric cancer;    MSI;    Next generation sequencing;    TMB;    EBV-encoded RNA;    PD-L1;   

DOI  :  10.1186/s13000-021-01099-y

来源: Springer

【 摘 要 】

ObjectivesGastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes have unique molecular features that may have different therapeutic methods. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in GC patients.MethodsThe data of 2504 GC patients, who underwent curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed. We analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS).ResultsMismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p = 0.000, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a intestinal group (p = 0.012), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%).ConclusionsUsing IHC and NGS, MSI status, protein expression, tumor mutation burden (TMB) and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

【 授权许可】

CC BY