胃食管腺癌中错配修复状态、化疗反应、生存与解剖部位的关系。
Relation between mismatch repair status, chemoresponse, survival and anatomic location in gastroesophageal adenocarcinoma.
机构信息
From the Department of Pathology, McGill University Health Centre, Montréal, Que. (Evaristo, Thai, Guiot, Camilleri-Broët, Marcus, Fiset); the Cancer Research Program and the LD MacLean Surgical Research Laboratories, Department of Surgery, Research Institute of the McGill University Health Centre, Montréal, Que. (Katz, Ramírez-GarcíaLuna, Sangwan, Mueller, Cools-Lartigue, Ferri); the Research Institute of the McGill University Health Centre, Montréal, Que. (Issac, Bertos); and the Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Centre, Montreal General Hospital, Montréal, Que. (Sangwan, Mueller, Cools-Lartigue, Ferri).
From the Department of Pathology, McGill University Health Centre, Montréal, Que. (Evaristo, Thai, Guiot, Camilleri-Broët, Marcus, Fiset); the Cancer Research Program and the LD MacLean Surgical Research Laboratories, Department of Surgery, Research Institute of the McGill University Health Centre, Montréal, Que. (Katz, Ramírez-GarcíaLuna, Sangwan, Mueller, Cools-Lartigue, Ferri); the Research Institute of the McGill University Health Centre, Montréal, Que. (Issac, Bertos); and the Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Centre, Montreal General Hospital, Montréal, Que. (Sangwan, Mueller, Cools-Lartigue, Ferri)
出版信息
Can J Surg. 2023 Feb 15;66(1):E79-E87. doi: 10.1503/cjs.017021. Print 2023 Jan-Feb.
BACKGROUND
It has recently been reported that mismatch repair (MMR) status and microsatellite instability (MSI) status in gastroesophageal carcinomas predict surgical, chemotherapeutic and immunotherapeutic outcomes; however, there is extensive variability in the reported incidence and clinical implications of MMR/MSI status in gastroesophaegal adenocarcinomas. We characterized a Canadian surgical patient cohort with respect to MMR status, clinicopathologic correlates and anatomic tumour location.
METHODS
We investigated MMR and BRAF V600E status of gastroesophaegal adenocarcinomas in patients who underwent gastrectomy or esophagectomy with extended (D2) lymphadenectomy at a single centre between 2011 and 2019. We correlated patterns of MMR expression in the overall cohort and in anatomic location-defined subgroups with treatment response and overall survival using multivariate analysis.
RESULTS
In all, 226 cases of gastroesophaegal adenocarcinoma (63 esophageal, 98 gastroesophageal junctional and 65 gastric) were included. The MMR-deficient (dMMR) immunophenotype was found in 28 tumours (12.3%) (15 junctional [15.3%], 13 gastric [20.0%] and none of the esophageal). The majority (25 [89%]) of dMMR cases showed MLH1/PMS2 loss without concurrent BRAF V600E mutation. Two MSH2/ MSH6-deficient gastric tumours and 1 MSH6-deficient junctional tumour were detected. The pathologic response to preoperative chemotherapy was comparable in the dMMR and MMR-proficient (pMMR) cohorts. However, dMMR status was associated with significantly longer median overall survival than pMMR status (5.8 yr v. 2.4 yr, hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.06-3.46), particularly in junctional tumours (4.6 yr v. 1.9 yr, HR 2.97, 95% CI 1.27-6.94).
CONCLUSION
Our study shows that MMR status has at least prognostic value, which supports the need for biomarker testing in gastroesophageal adenocarcinomas, including junctional adenocarcinomas. This highlights the clinical significance of determining the MMR status in all adenocarcinomas of the upper gastrointestinal tract. Response to induction chemotherapy, however, was not influenced by MMR status.
背景
最近有报道称， mismatch repair (MMR) 状态和 microsatellite instability (MSI) 状态可预测胃食管腺癌的手术、化疗和免疫治疗结果；然而，胃食管腺癌中 MMR/MSI 状态的报道发生率和临床意义存在很大差异。我们对加拿大手术患者队列的 MMR 状态、临床病理相关性和解剖肿瘤位置进行了特征描述。
方法
我们研究了 2011 年至 2019 年间在一家中心接受胃切除术或食管切除术联合广泛（D2）淋巴结切除术的胃食管腺癌患者的 MMR 和 BRAF V600E 状态。我们使用多变量分析，将整体队列和解剖部位定义亚组中的 MMR 表达模式与治疗反应和总生存相关联。
结果
总共纳入了 226 例胃食管腺癌（63 例食管、98 例胃食管交界处和 65 例胃）。在 28 例肿瘤（12.3%）中发现了 MMR 缺陷（dMMR）免疫表型（15 例交界处[15.3%]，13 例胃[20.0%]，无一例食管）。大多数（25 [89%]）dMMR 病例显示 MLH1/PMS2 缺失，无并发 BRAF V600E 突变。检测到 2 例 MSH2/MSH6 缺陷性胃肿瘤和 1 例 MSH6 缺陷性交界处肿瘤。术前化疗的病理反应在 dMMR 和 MMR 阳性（pMMR）队列中相当。然而，dMMR 状态与较长的中位总生存期相关，优于 pMMR 状态（5.8 年 v. 2.4 年，风险比 [HR] 1.91，95%置信区间 [CI] 1.06-3.46），特别是在交界处肿瘤（4.6 年 v. 1.9 年，HR 2.97，95% CI 1.27-6.94）。
结论
我们的研究表明，MMR 状态至少具有预后价值，这支持在胃食管腺癌中进行生物标志物检测，包括交界处腺癌。这凸显了确定上消化道所有腺癌 MMR 状态的临床意义。然而，诱导化疗的反应不受 MMR 状态的影响。
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