切除阶段I-III腺癌中的ROS1融合：欧洲胸部肿瘤平台肺部项目的结果

ROS1 fusions in resected stage I-III adenocarcinoma: Results from the European Thoracic Oncology Platform Lungscape project

LUNG CANCER

影响因子:4.40000

分区:医学2区 / 肿瘤学3区呼吸系统3区

发表日期:2024 Aug

作者: Ernst-Jan M Speel, Urania Dafni, Erik Thunnissen, Jan Hendrik Rüschoff, Cathal O'Brien, Jacek Kowalski, Keith M Kerr, Lukas Bubendorf, Irene Sansano, Leena Joseph, Mark Kriegsmann, Atilio Navarro, Kim Monkhorst, Line Bille Madsen, Javier Hernandez Losa, Wojciech Biernat, Albrecht Stenzinger, Andrea Rüland, Lisa M Hillen, Nesa Marti, Miguel A Molina-Vila, Tereza Dellaporta, Roswitha Kammler, Solange Peters, Rolf A Stahel, Stephen P Finn, Teodora Radonic,

摘要

ROS1融合是相对较低的患病率（0.6-2.0％），但在肺腺癌（LUAD）中具有靶向驱动力。希望筛查潜在融合这种融合的患者，需要进行鲁棒和低成本测试，例如免疫组织化学（IHC）。目的是研究使用IHC筛查的临床注释的欧洲I-III LUAD阶段中ROS1融合的普遍性，该筛选具有体外诊断（IVD）标记的克隆SP384（IVD）标记的克隆SP384，然后在预定的luAD中构建的螺旋式cloads-scressional cornersational conserceation serviental insune scressuty scressune scressune scrience ins1 clone 1 rous 1 ros1 ros1 ros1 scressy scressy scressy scressy scressy scressy scressy scrone 4套件和Ventana免疫染色器。外部质量控制后，训练有素的病理学家进行了分析。至少2+（任何百分比的肿瘤细胞）的染色强度被认为是IHC阳性（ROS1 IHC+）。随后，ROS1 IHC+病例为1：1：1与IHC0和IHC1+病例匹配，并经过正交ROS1 FISH和基于RNA的测试。阳性ROS1表达（ROS1 IHC+）的流行率定义为IHC 2+/3+，为4％（866 LuAds）。通过基于FISH/RNA的测试分析了28个ROS1 IHC+病例，其中只有两个带有确认的ROS1基因融合，对应于ROS1基因融合的下限0.23％。它们代表了7％的概率，可以识别ROS1 IHC+病例中的融合。这两种确认的病例都是仅有足够材料和H得分≥200的四个病例之一，导致50％的概率在H-SCORE被认为强烈阳性的情况下鉴定ROS1基因融合。通过基于鱼/RNA的测试，所有匹配的ROS1 IHC-（IHC0和IHC1+）病例也被发现为阴性，导致ROS1 IHC病例缺乏ROS1融合的可能性为100％。使用SP384克隆的ROS1 IHC可用于排除ROS1基因融合阴性病例。

Abstract

ROS1 fusion is a relatively low prevalence (0.6-2.0%) but targetable driver in lung adenocarcinoma (LUAD). Robust and low-cost tests, such as immunohistochemistry (IHC), are desirable to screen for patients potentially harboring this fusion. The aim was to investigate the prevalence of ROS1 fusions in a clinically annotated European stage I-III LUAD cohort using IHC screening with the in vitro diagnostics (IVD)-marked clone SP384, followed by confirmatory molecular analysis in pre-defined subsets.Resected LUADs constructed in tissue microarrays, were immunostained for ROS1 expression using SP384 clone in a ready-to-use kit and Ventana immunostainers. After external quality control, analysis was performed by trained pathologists. Staining intensity of at least 2+ (any percentage of tumor cells) was considered IHC positive (ROS1 IHC + ). Subsequently, ROS1 IHC + cases were 1:1:1 matched with IHC0 and IHC1 + cases and subjected to orthogonal ROS1 FISH and RNA-based testing.The prevalence of positive ROS1 expression (ROS1 IHC + ), defined as IHC 2+/3+, was 4 % (35 of 866 LUADs). Twenty-eight ROS1 IHC + cases were analyzed by FISH/RNA-based testing, with only two harboring a confirmed ROS1 gene fusion, corresponding to a lower limit for the prevalence of ROS1 gene fusion of 0.23 %. They represent a 7 % probability of identifying a fusion among ROS1 IHC + cases. Both confirmed cases were among the only four with sufficient material and H-score ≥ 200, leading to a 50 % probability of identifying a ROS1 gene fusion in cases with an H-score considered strongly positive. All matched ROS1 IHC- (IHC0 and IHC1 + ) cases were also found negative by FISH/RNA-based testing, leading to a 100 % probability of lack of ROS1 fusion for ROS1 IHC- cases.The prevalence of ROS1 fusion in an LUAD stage I-III European cohort was relatively low. ROS1 IHC using SP384 clone is useful for exclusion of ROS1 gene fusion negative cases.