Clinicopathological and prognostic features of Epstein‐Barr virus infection, microsatellite instability, and PD‐L1 expression in gastric cancer

摘要

Background and Objectives Gastric cancer (GC) has recently been categorized in molecular subtypes, which include Epstein‐Barr (EBV)‐positive and microsatellite instability (MSI) tumors. This distinction may provide prognostic information and identifies therapeutic targets. The aim of this study was to evaluate EBV, MSI, and PD‐L1 immunoexpression in GC and its relationship with clinicopathological characteristics and patient's prognosis. Methods We evaluated 287 GC patients who underwent D2‐gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD‐L1, and in situ hybridization for EBV detection utilizing tissue microarray. Results EBV‐positive and MSI were identified in 10.5% and 27% of the GCs, respectively. EBV positivity was associated to male gender ( P ?=?0.032), proximal location ( P ??0.001), undetermined Lauren type ( P ??0.001), poorly differentiated histology ( P ?=?0.043) and severe inflammatory infiltrate ( P ??0.001). MSI‐tumors were associated to older age ( P ?=?0.002), subtotal gastrectomy ( P ?=?0.004), pN0 ( P ?=?0.024) and earlier TNM stage ( P ?=?0.020). PD‐L1‐positive was seen in 8.8% of cases, with predominant expression in EBV‐positive GC ( P ??0.001). MSI was associated to better survival outcomes. Conclusion EBV‐positive GCs had increased PD‐L1 expression, while MSI GC had better survival outcome. EBV and MSI subgroups are distinct GC entities, their recognition is feasible by conventional techniques, and it may help individualize follow‐up and guide adjuvant therapy.