Service de gastro entérologie, Hôpital Saint Louis, AP-HP, Paris, France.
Unité d'oncologie moléculaire, Hôpital Saint Louis, AP-HP, Paris, France.
Clin Res Hepatol Gastroenterol. 2021 Jul;45(4):101691. doi: 10.1016/j.clinre.2021.101691. Epub 2021 Apr 20.
The prevalence and prognosis association of microsatellite instability (MSI) in oesogastric junction and gastric adenocarcinoma (OGC) have been reported with conflicting results.
Patients with OGC from 2010 to 2015 were enrolled in this retrospective multicenter study. MSI was determined by genotyping. MLH1 promoter methylation and BRAFV600E mutation were screened in the MSI tumors.
Among 315 tumors analyzed, 39 (12.4%) were of the MSI phenotype. Compared to MSS tumors, MSI tumors were more frequent in patients >70 years (17% vs 9%, p=0.048) and in gastric antral primary (20% versus 5% in junction tumor and 12% in fundus tumor. Among 29 MSI tumors analyzed, 28 had a loss of MLH1 protein expression and 27 had MLH1 promotor hypermethylation. None had a BRAF V600E mutation. The 4-year cumulative incidence of recurrence for patients with resected tumor was significantly lower in dMMR tumors versus pMMR tumors (17% versus 47%, p=0.01). For the patients with unresectable tumor the median overall survival was 11 months in MSS group and 14 months in MSI group (p=0.24).
MSI prevalence in OGC was 12.4%, associated with antral localization and advanced age. Patients with MSI tumors had a lower cumulative incidence of recurrence after surgery. MSI phenotype was mainly associated with loss of MLH1 protein expression, MLH1 promotor hypermethylation and had no BRAFV600E mutation.
胃食管结合部和胃腺癌（OGC）中微卫星不稳定性（MSI）的流行率和预后相关性已有报道，但结果相互矛盾。
本回顾性多中心研究纳入了 2010 年至 2015 年的 OGC 患者。通过基因分型确定 MSI，筛选 MSI 肿瘤中的 MLH1 启动子甲基化和 BRAFV600E 突变。
在分析的 315 个肿瘤中，有 39 个（12.4%）为 MSI 表型。与 MSS 肿瘤相比，MSI 肿瘤在>70 岁的患者中更为常见（17%比 9%，p=0.048），在胃窦原发性肿瘤中更为常见（20%比结合部肿瘤的 5%和胃底肿瘤的 12%）。在分析的 29 个 MSI 肿瘤中，28 个肿瘤 MLH1 蛋白表达缺失，27 个肿瘤 MLH1 启动子高度甲基化，无 BRAF V600E 突变。与 pMMR 肿瘤相比，MSI 肿瘤患者切除肿瘤的 4 年累积复发率显著降低（17%比 47%，p=0.01）。对于不可切除肿瘤的患者，MSS 组的中位总生存期为 11 个月，MSI 组为 14 个月（p=0.24）。
OGC 中 MSI 的流行率为 12.4%，与胃窦部定位和高龄有关。MSI 肿瘤患者手术后累积复发率较低。MSI 表型主要与 MLH1 蛋白表达缺失、MLH1 启动子高度甲基化相关，无 BRAFV600E 突变。
