Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital, No.52 Fucheng Road Haidian District, Beijing, 100142, 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, Beijing, 100142, People's Republic of China.
Diagn Pathol. 2021 May 1;16(1):38. doi: 10.1186/s13000-021-01099-y.
Gastric 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.
The 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).
Mismatch 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%).
Using 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.
胃癌（GC）是全球第四常见的癌症类型。不同的 GC 亚型具有独特的分子特征，可能有不同的治疗方法。本研究旨在探讨 GC 患者中 Epstein-Barr 病毒（EBV）感染、微卫星不稳定性（MSI）状态、程序性死亡配体 1（PD-L1）表达和基因突变的情况。
回顾性分析了 2013 年至 2018 年在北京大学肿瘤医院接受根治性胃切除术和淋巴结清扫术的 2504 例 GC 患者的临床病理资料。分析了这些患者免疫组化（IHC）图谱相关的临床病理因素，并采用下一代测序（NGS）分析了基因改变。
错配修复缺陷（d-MMR）GC 患者表达 PD-L1 的概率更高（p=0.000，PD-L1 截断值=1%）。此外，2504 例胃癌患者中 EBV 阳性和 d-MMR 的比例分别为 4%和 6.9%。MLH1/PMS2 阴性病例数为 126 例（6%），MSH2/MSH6 阴性病例数为 14 例（0.9%）。d-MMR 状态与肠型（p=0.012）相关，但与肿瘤分化无关。此外，MSI 和 d-MMR GC 状态（分别通过 NGS 和 IHC 检测）一致性较高，d-MMR GC 患者的 MSI 率更高。在 MSI 患者中检测到了一些与 DNA 损伤修复相关的基因，包括 POLE、ETV6、BRCA 和 RNF43。在具有高肿瘤突变负担的患者中，最显著突变的基因是 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%）和 ATM（39.53%）。
本研究通过 IHC 和 NGS 鉴定了 GC 患者的 MSI 状态、蛋白表达、肿瘤突变负担（TMB）和遗传改变，为 GC 的未来临床治疗提供了理论依据。
