Importance  Mismatch repair (MMR) deficiency (MMRD) and microsatellite instability (MSI) are prognostic for survival in many cancers and for resistance to fluoropyrimidines in early colon cancer. However, the effect of MMRD and MSI in curatively resected gastric cancer treated with perioperative chemotherapy is unknown.

Objective  To examine the association among MMRD, MSI, and survival in patients with resectable gastroesophageal cancer randomized to surgery alone or perioperative epirubicin, cisplatin, and fluorouracil chemotherapy in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial.

Design, Setting, and Participants  This secondary post hoc analysis of the MAGIC trial included participants who were treated with surgery alone or perioperative chemotherapy plus surgery for operable gastroesophageal cancer from July 1, 1994, through April 30, 2002. Tumor sections were assessed for expression of the MMR proteins mutL homologue 1, mutS homologue 2, mutS homologue 6, and PMS1 homologue 2. The association among MSI, MMRD, and survival was assessed.

Main Outcomes and Measures  Interaction between MMRD and MSI status and overall survival (OS).

Results  Of the 503 study participants, MSI results were available for 303 patients (283 with microsatellite stability or low MSI [median age, 62 years; 219 males (77.4%)] and 20 with high MSI [median age, 66 years; 14 males (70.0%)]). A total of 254 patients had MSI and MMR results available. Patients treated with surgery alone who had high MSI or MMRD had a median OS that was not reached (95% CI, 11.5 months to not reached) compared with a median OS among those who had neither high MSI nor MMRD of 20.5 months (95% CI, 16.7-27.8 months; hazard ratio, 0.42; 95% CI, 0.15-1.15; P = .09). In contrast, patients treated with chemotherapy plus surgery who had either high MSI or MMRD had a median OS of 9.6 months (95% CI, 0.1-22.5 months) compared with a median OS among those who were neither high MSI nor MMRD of 19.5 months (95% CI, 15.4-35.2 months; hazard ratio, 2.18; 95% CI, 1.08-4.42; P = .03).

Conclusions and Relevance  In the MAGIC trial, MMRD and high MSI were associated with a positive prognostic effect in patients treated with surgery alone and a differentially negative prognostic effect in patients treated with chemotherapy. If independently validated, MSI or MMRD determined by preoperative biopsies could be used to select patients for perioperative chemotherapy.

重要性  错配修复 (MMR) 缺陷 (MMRD) 和微卫星不稳定性 (MSI) 可预测许多癌症的存活率和早期结肠癌对氟嘧啶的耐药性。然而，MMRD和MSI对围手术期化疗治愈性切除胃癌的影响尚不清楚。

目的  在医学研究委员会辅助胃输注化疗 (MAGIC) 试验中，研究随机接受单独手术或围手术期表柔比星、顺铂和氟尿嘧啶化疗的可切除胃食管癌患者的 MMRD、MSI 和生存率之间的关系。

设计、设置和参与者  MAGIC 试验的这项二次事后分析包括从 1994 年 7 月 1 日至 2002 年 4 月 30 日期间接受单独手术或围手术期化疗加手术治疗可手术胃食管癌的参与者。评估肿瘤切片的表达MMR 蛋白 mutL 同源物 1、mutS 同源物 2、mutS 同源物 6 和 PMS1 同源物 2。评估了 MSI、MMRD 和存活率之间的关联。

主要结果和测量  MMRD 和 MSI 状态与总生存期 (OS) 之间的相互作用。

结果  在 503 名研究参与者中，MSI 结果可用于 303 名患者（283 名微卫星稳定性或低 MSI [中位年龄，62 岁；219 名男性（77.4%）] 和 20 名高 MSI [中位年龄，66 岁；14 名男性(70.0%)])。共有 254 名患者获得了 MSI 和 MMR 结果。MSI 或 MMRD 高的单独接受手术治疗的患者的中位 OS 未达到（95% CI，11.5 个月未达到），而 MSI 和 MMRD 均未达到的患者中位 OS 为 20.5 个月（95% CI，16.7-27.8 个月；风险比，0.42；95% CI，0.15-1.15；P = .09)。相比之下，高 MSI 或 MMRD 接受化疗加手术治疗的患者的中位 OS 为 9.6 个月（95% CI，0.1-22.5 个月），而非高 MSI 或 MMRD 的中位 OS 为 19.5 个月（95% CI，15.4-35.2 个月；风险比，2.18；95% CI，1.08-4.42；P  = .03）。

结论和相关性  在 MAGIC 试验中，MMRD 和高 MSI 与单独接受手术治疗的患者的阳性预后作用和接受化疗的患者的不同的阴性预后作用相关。如果经过独立验证，通过术前活检确定的 MSI 或 MMRD 可用于选择患者进行围手术期化疗。