Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA.
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea.
Pathol Res Pract. 2020 Apr;216(4):152881. doi: 10.1016/j.prp.2020.152881. Epub 2020 Feb 13.
The programmed death receptor ligand 1 (PD-L1) immunohistochemistry (IHC) 22C3 pharmDx assay is a widely used selection method for pembrolizumab treatment in gastric cancer (GC) patients, especially in the U.S. The present study investigated the relationship between PD-L1 expression and the clinical features, molecular markers, and molecular subtypes of GC.
PD-L1 expression was assessed based on combined positive score (CPS) using PD-L1 IHC 22C3 pharmDx in the Asian Cancer Research Group (ACRG) GC cohort (N = 300), which has been previously genomically profiled. PD-L1 positivity was defined as PD-L1 CPS ≥ 1. The association between PD-L1 expression and clinical features, tumor burden, and molecular subtypes (ACRG and The Cancer Genome Atlas [TCGA]) was analyzed.
Of the 300 tumors, 178 (59.3 %) had PD-L1 CPS ≥ 1 and 122 (40.7 %) had PD-L1 CPS < 1. PD-L1 CPS ≥ 1 was significantly associated with stage I tumor (P = 0.022), high microsatellite instability (MSI-H) (P < 0.001), Epstein-Barr virus (EBV) positivity (P = 0.008), and positive Helicobacter pylori status (P = 0.001). PD-L1 CPS ≥ 1 was observed in 96/193 (49.7 %) EBV-negative/microsatellite stable (MSS) tumors. In gene expression profiling, PD-L1 CPS was highly correlated with mutational load (P < 0.001) as well as EBV (P < 0.001) and MSI subtypes (P < 0.001); 27/300 (9%) GC patients had a very high PD-L1 (≥ 20) score (MSI-H, n = 10; EBV, n = 6; and non-EBV/MSS, n = 11). OS was longer in patients with PD-L1 CPS ≥ 1 tumors than in those with PD-L1 CPS < 1 tumors (median OS not reached vs. 40 months; P = 0.008; log-rank test).
PD-L1 is expressed in 59.3 % of GC patients and is associated with MSI and EBV positivity. These results provide a basis for identifying GC patients who may benefit from anti-PD-1/PD-L1 therapy.
程序性死亡受体配体 1（PD-L1）免疫组化（IHC）22C3 pharmDx 检测被广泛用于选择接受 pembrolizumab 治疗的胃癌（GC）患者，尤其是在美国。本研究旨在探讨 PD-L1 表达与 GC 的临床特征、分子标志物和分子亚型之间的关系。
采用 PD-L1 IHC 22C3 pharmDx 检测试剂盒，根据联合阳性评分（CPS）评估亚洲癌症研究组（ACRG）GC 队列（n=300）中 PD-L1 的表达情况，该队列此前已进行了基因组分析。PD-L1 阳性定义为 PD-L1 CPS≥1。分析了 PD-L1 表达与临床特征、肿瘤负担和分子亚型（ACRG 和癌症基因组图谱[TCGA]）之间的关系。
在 300 例肿瘤中，178 例（59.3%）的 PD-L1 CPS≥1，122 例（40.7%）的 PD-L1 CPS<1。PD-L1 CPS≥1与Ⅰ期肿瘤（P=0.022）、高微卫星不稳定性（MSI-H）（P<0.001）、EBV 阳性（P=0.008）和幽门螺杆菌阳性状态（P=0.001）显著相关。在 193 例 EBV 阴性/MSS 肿瘤中，有 96/193（49.7%）的肿瘤 PD-L1 CPS≥1。在基因表达谱分析中，PD-L1 CPS 与突变负荷高度相关（P<0.001），也与 EBV（P<0.001）和 MSI 亚型相关（P<0.001）；300 例 GC 患者中有 27 例（9%）的 PD-L1 评分很高（≥20）（MSI-H，n=10；EBV，n=6；非 EBV/MSS，n=11）。PD-L1 CPS≥1 肿瘤患者的 OS 长于 PD-L1 CPS<1 肿瘤患者（中位 OS 未达到 vs. 40 个月；P=0.008；对数秩检验）。
PD-L1 在 59.3%的 GC 患者中表达，并与 MSI 和 EBV 阳性相关。这些结果为识别可能从抗 PD-1/PD-L1 治疗中获益的 GC 患者提供了依据。
