National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Lanzhou University Second Hospital, Lanzhou, People's Republic of China.
Oncologist. 2023 Oct 3;28(10):e891-e901. doi: 10.1093/oncolo/oyad108.
To date, the role of deficient mismatch repair (dMMR) remains to be proven in gastric cancer, and it is difficult to judge its value in clinical application. Our study aimed to investigate how MMR status affected the prognosis in patients with gastrectomy, as well as the efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with dMMR with gastric cancer.
Patients with gastric cancer with certain pathologic diagnosis of dMMR or proficient MMR (pMMR) using immunohistochemistry from 4 high-volume hospitals in China were included. Propensity score matching was used to match patients with dMMR or pMMR in 1:2 ratios. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models based on hazard ratios (HRs) and 95% confidence intervals (CIs) were used to determine the risk factors for survival.
In total, data from 6176 patients with gastric cancer were ultimately analyzed, and loss of expression of one or more MMR proteins was observed in 293 patients (293/6176, 4.74%). Compared to patients with pMMR, patients with dMMR are more likely to be older (≥66, 45.70% vs. 27.94%, P < .001), distal location (83.51% vs. 64.19%, P < .001), intestinal type (42.21% vs. 34.46%, P < .001), and in the earlier pTNM stage (pTNM I, 32.79% vs. 29.09%, P = .009). Patients with gastric cancer with dMMR showed better OS than those with pMMR before PSM (P = .002); however, this survival advantage was not observed for patients with dMMR after PSM (P = .467). As for perioperative chemotherapy, results of multivariable Cox regression analysis showed that perioperative chemotherapy was not an independent prognostic factor for PFS and OS in patients with dMMR with gastric cancer (HR = 0.558, 95% CI, 0.270-1.152, P = .186 and HR = 0.912, 95% CI, 0.464-1.793, P = .822, respectively).
In conclusion, perioperative chemotherapy could not prolong the OS and PFS of patients with dMMR with gastric cancer.
迄今为止，错配修复缺陷（dMMR）在胃癌中的作用仍有待证实，其在临床应用中的价值难以判断。本研究旨在探讨 MMR 状态如何影响接受胃切除术患者的预后，以及 dMMR 型胃癌患者新辅助化疗和辅助化疗的疗效。
本研究纳入了来自中国 4 家高容量医院的经免疫组织化学检测明确为 dMMR 或 proficient MMR（pMMR）的胃癌患者。采用倾向性评分匹配（PSM）将 dMMR 或 pMMR 患者以 1:2 的比例进行匹配。采用 Kaplan-Meier 法绘制总生存（OS）和无进展生存（PFS）曲线，并采用对数秩检验进行统计学比较。采用基于风险比（HR）和 95%置信区间（CI）的单因素和多因素 Cox 比例风险模型确定生存的危险因素。
本研究最终分析了 6176 例胃癌患者的数据，其中 293 例（293/6176，4.74%）患者存在一种或多种 MMR 蛋白表达缺失。与 pMMR 患者相比，dMMR 患者更有可能年龄较大（≥66 岁，45.70%比 27.94%，P<0.001）、肿瘤位置更靠远端（83.51%比 64.19%，P<0.001）、组织学分型为肠型（42.21%比 34.46%，P<0.001），且处于更早的 pTNM 分期（pTNM I 期，32.79%比 29.09%，P=0.009）。在 PSM 之前，dMMR 型胃癌患者的 OS 优于 pMMR 型患者（P=0.002）；然而，在 PSM 之后，dMMR 型患者的生存优势并不明显（P=0.467）。对于围手术期化疗，多变量 Cox 回归分析结果表明，围手术期化疗不是 dMMR 型胃癌患者 PFS 和 OS 的独立预后因素（HR=0.558，95%CI，0.270-1.152，P=0.186 和 HR=0.912，95%CI，0.464-1.793，P=0.822，分别）。
综上所述，围手术期化疗不能延长 dMMR 型胃癌患者的 OS 和 PFS。
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