OBJECTIVE Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (≤45 years) compared with an average-onset cohort (≥55 years) and characterize the clinicopathologic pattern of young-onset GC. METHODS Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records. RESULTS Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p = 0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p = 0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68 years). MSI-H was found only in the average-onset cohort [0% vs 27%, p = 0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p = 0.002). CONCLUSION Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.

中文翻译：

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年轻人型胃癌和爱泼斯坦-巴尔病毒（EBV）-发病机理的主要参与者？

目的胃癌（GC）是癌症死亡的主要原因，主要发生在老年，年轻患者的发病率增加。癌症基因组图谱指出了GC的四种亚型，其中爱泼斯坦-巴尔病毒（EBV）亚型估计为8.7％。我们旨在确定与平均发病队列（≥55岁）相比，年轻的GC患者（≤45岁）的EBV亚型患病率，并表征年轻发病的GC的临床病理模式。方法采用qPCR方法对两个队列的患者的胃癌样本进行EBV筛查。对人表皮生长因子受体2（HER2），微卫星不稳定性（MSI）状态和程序性死亡配体1（PD-L1）进行了另外的染色。从医疗记录中检索人口统计资料和临床数据。结果回顾了39例年轻发病和35例平均发病的GC患者。队列之间的肿瘤位置，家族史，组织学和HER2状态没有明显差异。被诊断为转移性疾病的年轻患者更多（27％比9％，p = 0.0498）。EBV在年轻人群中更为普遍（33％比11％，p = 0.025）。在美国（68岁），有15/17 EBV阳性患者的确诊为GC中位年龄。仅在平均发病队列中发现了MSI-H [0％对27％，p = 0.001）。在年轻发病人群中PD-L1阳性较高（31％vs 3％，p = 0.002）。结论我们的研究表明EBV亚型在年轻发作的GC中更为普遍，并且可能在发病机理中起关键作用。年轻发作的GC中较高的PD-L1阳性率可以改变治疗策略。