Lee Sun Mi, Oh Hyunjoo
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W. 11th street, Indianapolis, IN, 46202, USA.
Department of Pathology, Jeju National University Hospital, Jeju-si, South Korea.
Sci Rep. 2024 Dec 28;14(1):30932. doi: 10.1038/s41598-024-81764-6.
Gastric carcinoma with lymphoid stroma (GCLS) is characterized by dense intra-and peritumoral lymphocytic infiltration and a high rate of Epstein Barr Virus (EBV) infection, suggesting being a promising candidate for immunotherapy. We investigated correlations between PD-L1 expression and clinicopathologic factors, including EBV positivity and microsatellite instability (MSI) status in GCLSs. The study included resected 214 GCLSs and 300 gastric adenocarcinomas (GACs) for control. Epstein Barr Virus encoding region in situ hybridization (EBER ISH), immunohistochemistry for PD-L1 and HER2, dual-colored in situ hybridization for HER2, and MSI analysis were performed. EBV positivity was found in 181 (85%) of 214 GCLSs. MSI analysis demonstrated that 0.6% of EBV + GCLSs and 54.5% of EBV-GCLSs were MSI-high compared to 7% of EBV-GACs. Approximately 3% and 3.9% of HER2 amplifications were found in EBV- and EBV + GCLSs compared to 13% of EBV-GACs. PD-L1 expression with ≥ 1, ≥ 5, and ≥ 10 combined positive scores (CPS) were observed in 81.8%, 70.2%, and 55.3% of EBV + GCLSs. PD-L1 expression with ≥ 10 CPS was observed in 21.2% of EBV-GCLSs, predominantly in MSI-H tumors (85.7%). EBV positivity and MSI are associated with PD-L1 positivity rates in patients with GCLS who may respond better to PD-1/PD-L1 inhibitors but not anti-HER2 inhibitors.
伴有淋巴样间质的胃癌（GCLS）的特征是肿瘤内和肿瘤周围有密集的淋巴细胞浸润以及较高的爱泼斯坦-巴尔病毒（EBV）感染率，提示其可能是免疫治疗的理想候选对象。我们研究了GCLS中程序性死亡受体配体1（PD-L1）表达与临床病理因素之间的相关性，包括EBV阳性和微卫星不稳定性（MSI）状态。该研究纳入了214例接受手术切除的GCLS和300例胃腺癌（GAC）作为对照。进行了EBV编码区原位杂交（EBER ISH）、PD-L1和人表皮生长因子受体2（HER2）免疫组织化学、HER2双色原位杂交以及MSI分析。在214例GCLS中，181例（85%）为EBV阳性。MSI分析显示，与7%的EBV阴性GAC相比，EBV阳性GCLS中有0.6%为高度微卫星不稳定（MSI-H），EBV阴性GCLS中有54.5%为MSI-H。与13%的EBV阴性GAC相比，EBV阴性和EBV阳性GCLS中HER2扩增率分别约为3%和3.9%。在EBV阳性GCLS中，PD-L1表达联合阳性评分（CPS）≥1、≥5和≥10的分别占81.8%、70.2%和55.3%。在EBV阴性GCLS中，21.2%的病例PD-L1表达CPS≥10，主要见于MSI-H肿瘤（85.7%）。EBV阳性和MSI与GCLS患者的PD-L1阳性率相关，这类患者可能对程序性死亡受体1（PD-1）/PD-L1抑制剂反应更好，但对抗HER2抑制剂反应不佳。
