On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas
On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas
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DOI：
10.1016/j.lungcan.2013.11.019
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发表时间：
2014-02-01
期刊：
影响因子：
5.3
通讯作者：
McLeer-Florin, Anne
中科院分区：
文献类型：
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作者：
Mescam-Mancini, Lenaig;Lantuejoul, Sylvie;McLeer-Florin, Anne
目的：ROS1 原癌基因易位定义了非小细胞肺癌 (NSCLC) 中的一个新分子亚组，并且与 MET/ALK 抑制剂克唑替尼的反应相关。这些重排在 0.9-1.7% 的 NSCLC、野生型 EGFR、KRAS 和 ALK（“三阴性”）肺腺癌中有所描述。因此，快速有效地识别这些改变变得越来越重要。 材料和方法：在本研究中，通过使用 ROS1 D4D6 抗体的 IHC 和使用两种市售 ROS1 断裂探针的 FISH 筛选了 121 例三阴性肺腺癌。为了解决 ROS1 抗体与其他蛋白激酶受体可能存在的交叉反应性，我们筛查了另外 80 例已知有 EGFR、KRAS、PI3KCA、BRAF、HER2 突变或 ALK 重排的病例。 结果：我们诊断出 9 例 ROS1 重排腺癌，FISH 结果呈阳性（51-87% 细胞核重排），IHC 染色呈阳性 （2+/3+ 细胞质染色）。只有一个 ROS1 阳性 FISH 病例具有经典的分裂模式，其他病例则显示出变异模式，最常见的是 5' 端粒探针丢失。考虑到 2+ 染色细胞的阳性阈值，ROS1 D4D6 抗体与 FISH 相比的敏感性为 100%，特异性为 96.9%，因为两个 HER2 突变肿瘤的 D4D6 抗体呈阳性，FISH 中没有任何易位。所有 ROS1 阳性病例均处于晚期，发生于从不吸烟或轻度吸烟者中。主要为实性筛状腺癌和腺泡腺癌，其中印戒细胞5例，钙化3例。一个阳性病例是浸润性粘液癌。 结论：我们的结果表明，基于 ROS1 融合蛋白 IHC 检测的筛查算法（通过 ROS1 分离 FISH 检测确认阳性或可疑）适用于晚期“三阴性”肺腺癌，因为在我们的系列中，该选定人群中 ROS1 阳性病例的患病率达到 7.4%。 (C) 2013 Elsevier Ireland Ltd. 保留所有权利。
Objectives: ROS1 proto-oncogene translocations define a new molecular subgroup in non-small cell lung cancers (NSCLC) and are associated with a response to the MET/ALK inhibitor, crizotinib. These rearrangements are described in 0.9-1.7% NSCLC, in wild-type EGFR, KRAS and ALK ("triple negative") lung adenocarcinomas. Rapid and efficient identification of these alterations is thus becoming increasingly important.Materials and methods: In this study, 121 triple negative lung adenocarcinomas were screened by both IHC with the ROS1 D4D6 antibody, and FISH using two commercially available ROS1 break-apart probes. To address a possible cross-reactivity of the ROS1 antibody with other protein kinase receptors, we screened 80 additional cases with known EGFR, KRAS, PI3KCA, BRAF, HER2 mutations or ALK-rearrangement.Results: We diagnosed 9 ROS1-rearranged adenocarcinomas, with both a positive FISH result (51-87% rearranged nuclei) and a positive IHC staining (2+/3+ cytoplasmic staining). Only one of the ROS1-positive FISH cases was characterized by a classical split pattern, the others showed a variant pattern, most commonly involving a loss of the 5' telomeric probe. Considering a positivity threshold of 2+ stained cells, the sensitivity of the ROS1 D4D6 antibody compared to FISH was 100% and the specificity 96.9%, as two HER2-mutated tumors were positive with D4D6 antibody, without any translocation in FISH. All the ROS1-positive cases were at an advanced stage, arising in never or light smokers. They were mainly solid cribriform and acinar adenocarcinomas, with signet ring cells noted in 5 cases, and calcifications in 3 cases. One positive case was an invasive mucinous carcinoma.Conclusion: Our results show that a screening algorithm based on an IHC detection of ROS1 fusion proteins, confirmed if positive or doubtful by a ROS1 break-apart FISH assay, is pertinent in advanced "triple negative" lung adenocarcinomas, since the prevalence of ROS1-positive cases in this selected population reaches 7.4% in our series. (C) 2013 Elsevier Ireland Ltd. All rights reserved.