Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Gastric Surgery Division, National Cancer Center Hospital East, Chiba, Japan.
Ann Surg Oncol. 2023 Aug;30(8):5227-5236. doi: 10.1245/s10434-023-13266-0. Epub 2023 Mar 19.
The aim of this study was to investigate the prognostic impact of mismatch repair (MMR) status, programmed death-ligand 1 (PD-L1) expression, and Epstein-Barr virus (EBV) status in stage II/III gastric cancer after surgery.
This study included 679 patients diagnosed with pathological stage II/III gastric cancer who underwent curative gastrectomy followed by adjuvant chemotherapy (AC) or observation between 2007 and 2015. Clinical outcomes were retrospectively reviewed and compared with stratification by AC and other clinicopathological factors.
Patients were divided into AC (n = 484) or surgery alone (SA; n = 195) groups and were further stratified by MMR and EBV status: MMR-deficient (DMMR) and MMR-proficient (PMMR) groups. Comparing the AC-DMMR group versus the AC-PMMR group, 5-year overall survival was 92.0% versus 74.0% (log-rank p < 0.01), and comparing the SA-DMMR group versus the SA-PMMR group, 5-year overall survival was 71.1% versus 73.7% (log-rank p = 0.89). DMMR (hazard ratio 0.25, 95% confidence interval 0.07-0.81) was identified as an independent prognostic factor in the AC group but not in the SA group. In the subgroup analysis, PD-L1-negative patients among the EBV-positive patients or in the DMMR group had a poor prognosis in both the AC and SA groups. The prognosis of the PMMR and EBV-negative patients was similar regardless of PD-L1 expression.
DMMR was associated with a favorable prognosis in stage II/III gastric cancer after surgery and adjuvant therapy. PD-L1 expression may affect the prognosis of DMMR and EBV-positive gastric cancer.
本研究旨在探讨手术治疗后 II 期/III 期胃癌患者错配修复（MMR）状态、程序性死亡配体 1（PD-L1）表达和 Epstein-Barr 病毒（EBV）状态的预后影响。
本研究纳入了 2007 年至 2015 年间接受根治性胃切除术和辅助化疗（AC）或观察治疗的病理 II 期/III 期胃癌患者 679 例。回顾性分析临床结果，并按 AC 和其他临床病理因素分层进行比较。
患者分为 AC（n=484）或单纯手术（SA；n=195）组，并按 MMR 和 EBV 状态进一步分层：错配修复缺陷（DMMR）和错配修复功能完整（PMMR）组。与 AC-DMMR 组相比，AC-PMMR 组 5 年总生存率为 92.0% vs 74.0%（log-rank p<0.01），与 SA-DMMR 组相比，SA-PMMR 组 5 年总生存率为 71.1% vs 73.7%（log-rank p=0.89）。DMMR（危险比 0.25，95%置信区间 0.07-0.81）被确定为 AC 组的独立预后因素，但不是 SA 组的独立预后因素。亚组分析显示，EBV 阳性患者或 DMMR 组中 PD-L1 阴性患者在 AC 和 SA 组中预后均较差，而 PMMR 和 EBV 阴性患者无论 PD-L1 表达如何，其预后相似。
DMMR 与手术和辅助治疗后 II 期/III 期胃癌的良好预后相关。PD-L1 表达可能影响 DMMR 和 EBV 阳性胃癌的预后。
