Young-onset gastric cancer and Epstein-Barr Virus (EBV) - a major player in the pathogenesis?
Young-onset gastric cancer and Epstein-Barr Virus (EBV) - a major player in the pathogenesis?
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DOI：
10.1186/s12885-020-6517-0
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发表时间：
2020-01-14
期刊：
影响因子：
3.8
通讯作者：
Aharon, Irit Ben
中科院分区：
文献类型：
--
作者：
Moore, Assaf;Hikri, Elad;Aharon, Irit Ben
目的胃癌（GC）是癌症死亡的主要原因，主要发生在老年人中，年轻患者的发病率呈上升趋势。癌症基因组图谱显示胃癌有4种亚型，其中EBV亚型估计占8.7%。我们的目的是确定EBV亚型在年轻GC患者（= 55岁）中的患病率，并描述年轻发病GC的临床病理模式。方法采用qPCR方法对两组胃癌患者进行EBV检测。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）进行额外染色。从医疗记录中检索人口统计数据和临床数据。结果回顾性分析了39例年轻起病胃癌患者和35例平均起病胃癌患者。两组患者的肿瘤位置、家族史、组织学及HER2水平无明显差异。更多的年轻发病患者被诊断为转移性疾病（27% vs 9%, p = 0.0498）。EBV在年轻发病队列中更为普遍（33% vs 11%, p = 0.025）。在美国，EBV阳性患者中有15/17低于GC诊断的中位年龄（68岁）。MSI-H仅在平均发病队列中发现[0% vs 27%， p = 0.001]。PD-L1阳性在年轻发病队列中较高（31% vs 3%, p = 0.002）。结论EBV亚型在年轻发病的胃癌中更为普遍，并可能在其发病机制中起关键作用。年轻发病的GC中较高的PD-L1阳性率可能改变治疗策略。我们目前正在一项前瞻性试验中评估这些发现。
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 (= 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.