摘要
具有淋巴样间质的胃癌是一种罕见的变异型,富含互斥的EB病毒(Epstein-Barr virus, EBV)和错配修复 (mismatch repair, MMR)缺陷。我们进行这项研究以评估这一形态学同质性肿瘤亚型的分子变化,同时将它们与癌症基因图谱研究中的295例传统胃癌进行对比分析。我们确定了31例研究病例,并对它们进行EBV编码的RNA原位杂交,同时评估MMR状态。对PD-L1、β-连蛋白和HER2进行免疫染色;使用癌症综合检测谱对提取的DNA进行测序。研究中的大部分患者是处于I期或II期(76%)的老年男性。肿瘤被分为EBV+/MMR正常(MMR-P) (n=7)、EBV-/MMR缺陷(n=12)和EBV-/MMR-P(n=12)。EBV-/MMR-P肿瘤通常发生于近端胃(83%),并且呈现腺体分化的异质性生长方式(83%)。所有亚组肿瘤均表现为大量肿瘤浸润性淋巴细胞和高PD-L1表达,少有核β-连蛋白累积(10%),缺乏HER2膜染色和HER2扩増。与EBV-/MMR-P肿瘤(9%, P=0.05)相比, EBV-/MMR缺陷肿瘤的肿瘤突变负荷显著增加(P=0.001),KRAS发生变化(56%)。与EBV+/MMR正常(0%, P=0.01)和 EBV-/MMR缺陷肿瘤(11%, P<0.01)相比,TP53变异更常见于EBV-/MMR-P肿瘤(82%)。KRAS、ARIDRA、PIK3CA和TP53基因异常的分布方式与癌症基因组数据库相似。我们得出结论,具有淋巴样间质的胃癌具有一定的分子变化谱,并常表达PD-L1,提示此类肿瘤可能对免疫检查点抑制剂敏感和/或可用靶向酪氨酸激酶受体介导的信号通路的药物进行治疗。
关键词:二代测序,胃髓样癌,免疫应答,微卫星不稳定性,EB病毒
正文
杜艳茹 翻译 袁培(特邀)/应建明 审校
美国外科病理学杂志中文版第三期全文No.3
Am J Surg Pathol ;42:453-462
The American Journal of Surgical Pathology中文版声明:
© Wolters Kluwer Health
The material is published by Wolters Kluwer Health with the permission of American Journal of Surgical Pathology.No part of this publication may be reproduced in any form,stored in a retrieval system or transmitted in any form,by any means,without prior written permission from Wolters Kluwer Health.Opinions expressed by the authors and advertisers are not necessarily those of the American Journal of Surgical Pathology, its affiliates,or of the Publisher.The American Journal of Surgical Pathology,its affiliates,and the Publisher disclaim any liability to any party for the accuracy,completeness,efficacy,or availability of the material contained in this publication (including drug dosages) or for any damages arising out of the use or non-use of any of the material contained in this publication.
Although advertising material is expected to conform to ethical (medical) standards,inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer.
美国外科病理学杂志
中文版
如果觉得《美国外科病理学杂志 | 具有淋巴样间质的胃癌——一项组织病理学和分子特征的评估》对你有帮助,请点赞、收藏,并留下你的观点哦!