MET IHC Is a Poor Screen for MET Amplification or MET Exon 14 Mutations in Lung Adenocarcinomas: Data from a Tri-Institutional Cohort of the Lung Cancer Mutation Consortium
MET IHC Is a Poor Screen for MET Amplification or MET Exon 14 Mutations in Lung Adenocarcinomas: Data from a Tri-Institutional Cohort of the Lung Cancer Mutation Consortium
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DOI：
10.1016/j.jtho.2019.06.009
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发表时间：
2019-09-01
影响因子：
20.4
通讯作者：
Kris, Mark G.
中科院分区：
文献类型：
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作者：
Guo, Robin;Berry, Lynne D.;Kris, Mark G.
简介：肺癌中的MNNG HOS转化基因（MET）扩增和MET外显子14（METex 14）改变影响MET原癌基因受体酪氨酸激酶（MET [别名肝细胞生长因子受体]）抑制剂的敏感性。荧光原位杂交（FISH）、下一代测序（NGS）和免疫组织化学（IHC）已用于评价MET依赖性。在这里，我们已经确定了MET IHC与METex 14突变和MET amplification.Methods的关联：我们收集了来自肺癌突变联盟的三机构队列的数据。所有患者均患有转移性肺腺癌，既往未接受过靶向治疗。MET IHC阳性定义为使用SP 44抗体的H评分≥ 200。MET扩增的定义是使用NGS或MET-着丝粒7号染色体的比率大于2.2与使用FISH的拷贝数倍数变化为1.8倍或更多。结果：我们测试了来自181名患者的MET IHC，MET扩增和METex 14突变的组织。总体而言，181例患者中有71例（39%）为MET IHC阳性，181例患者中有3例（2%）为MET扩增，181例患者中有2例（1%）携带METex 14突变。在MET扩增的病例中，2例为FISH阳性，MET与7号染色体着丝粒的比值为3.1和3.3，1例为NGS阳性，倍数变化为4.4倍，3例中1例为MET IHC阳性。在71例IHC阳性病例中，1例（1%）为MET扩增，2例（3%）为METex 14突变。MET IHC阴性病例中，110例中有2例（2%）为MET扩增。结论：在这项研究中，几乎所有MET IHC阳性病例均为MET扩增或METex 14突变阴性。MET IHC也可能错过MET扩增的患者。该队列中MET扩增病例数量有限，因此证明MET免疫组化与MET扩增之间的关联具有挑战性。然而，IHC似乎是这些基因组变化的低效筛选。MET扩增或METex 14突变最好通过FISH和多重NGS面板检测。(C)2019年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
Introduction: MNNG HOS Transforming gene (MET) amplification and MET exon 14 (METex14) alterations in lung cancers affect sensitivity to MET proto-oncogene, receptor tyrosine kinase (MET [also known by the alias hepatocyte growth factor receptor]) inhibitors. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and immunohistochemistry (IHC) have been used to evaluate MET dependency. Here, we have determined the association of MET IHC with METex14 mutations and MET amplification.Methods: We collected data on a tri-institutional cohort from the Lung Cancer Mutation Consortium. All patients had metastatic lung adenocarcinomas and no prior targeted therapies. MET IHC positivity was defined by an H-score of 200 or higher using SP44 antibody. MET amplification was defined by copy number fold change of 1.8x or more with use of NGS or a MET-to-centromere of chromosome 7 ratio greater than 2.2 with use of FISH.Results: We tested tissue from 181 patients for MET IHC, MET amplification, and METex14 mutations. Overall, 71 of 181 patients (39%) were MET IHC-positive, three of 181 (2%) were MET-amplified, and two of 181 (1%) harbored METex14 mutations. Of the MET-amplified cases, two were FISH positive with MET-to-centromere of chromosome 7 ratios of 3.1 and 3.3, one case was NGS positive with a fold change of 4.4x, and one of the three cases was MET IHC-positive. Of the 71 IHC-positive cases, one (1%) was MET-amplified and two (3%) were METex14-mutated. Of the MET IHC-negative cases, two of 110 (2%) were MET-amplified.Conclusions: In this study, nearly all MET IHC-positive cases were negative for MET amplification or METex14 mutations. MET IHC can also miss patients with MET amplification. The limited number of MET-amplified cases in this cohort makes it challenging to demonstrate an association between MET IHC and MET amplification. Nevertheless, IHC appears to be an inefficient screen for these genomic changes. MET amplification or METex14 mutations can best be detected by FISH and a multiplex NGS panel. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.