Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and pathological implications
Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and pathological implications
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DOI：
10.1136/esmoopen-2018-000470
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发表时间：
2019-06-01
期刊：
影响因子：
7.3
通讯作者：
Cervantes, Andres
中科院分区：
文献类型：
--
作者：
Martinez-Ciarpaglini, Carolina;Fleitas-Kanonnikoff, Tania;Cervantes, Andres
背景：胃癌的分子分类识别出两种易于发生免疫检查点阻断的亚型：微卫星不稳定性肿瘤和EB病毒(EBV)相关肿瘤。本研究旨在评价免疫组织化学和聚合酶链式反应在评估微卫星状态方面的一致性，并探讨微卫星不稳定性(MSI)和EB病毒(EBV)作为预测生存因素的价值。材料与方法收集246例各期连续诊断的胃癌病例，应用免疫组织化学错配修复蛋白(MMR)和聚合酶链式反应(PCR)评估微卫星状态。结果45例(18%)MSI患者EBV阳性，13例(6%)EBV阳性。MSI与女性、高龄、远端部位和改良Lauren分类的远端非弥漫型有关。EBV表达以近端非弥漫型和近端非弥漫型最常见。免疫组织化学对微卫星检测的敏感性、特异性、阳性预测值和阴性预测值分别为91%、98%、91%和98%。在多因素分析中，MSI是I-III期肿瘤特异性生存(TSS)的独立预测因素(MSI：HR：0.37，95%CI为0.12~0.95，P=0.04)。结论MSI状态和EBV表达应纳入常规病理报告。首先，MSI定义了一个不同的病理实体，结果更好。其次，MSI和EBV可能是识别对免疫检查点阻断抑制剂有反应的患者的有用生物标志物。为此，MMR蛋白的免疫组织化学研究和EBV检测的原位杂交研究是可行且经济有效的方法。
Background The molecular classification of gastric cancer recognises two subtypes prone to immune checkpoint blockade: the microsatellite unstable and the Epstein-Barr virus (EBV)-related tumours. We aim to assess the concordance between immunohistochemistry and PCR for microsatellite status evaluation, and explore the value of microsatellite instability (MSI) and EBV as predictive survival factors.Material and methods We collected 246 consecutively diagnosed gastric cancer cases in all stages and evaluated the microsatellite status using immunohistochemistry for mismatched repair (MMR) proteins and PCR. EBV expression was studied through in situ hybridisation.Results Forty-five (18%) cases presented MSI and 13 (6%) were positive for EBV. MSI was associated with female sex, older age, distal location and distal nondiffuse type of the modified Lauren classification. EBV expression was most frequent in proximal location and proximal non-diffuse type. The sensitivity, specificity, positive predictive value and negative predictive value of immunohistochemistry for the microsatellite study were 91%, 98%, 91% and 98%, respectively. In the multivariate analysis, MSI was an independent predictor of favourable tumour-specific survival (TSS) in stages I-III (MSI: HR: 0.37, 95% CI 0.12 to 0.95, p= 0.04).Conclusions The MSI status and the EBV expression should be incorporated in routine pathological report for two reasons. First, MSI defines a different pathological entity with a better outcome. Second, MSI and EBV may be useful biomarkers to identify patients who will respond to immune checkpoint blockade inhibitors. For this purpose, immunohistochemical study for MMR proteins and in situ hybridisation study for EBV evaluation are feasible and cost-effective methods.