MET IHC 作为一种筛选肺腺癌 MET 扩增或 MET 外显子 14 突变的方法并不理想：来自肺癌突变联盟的三机构队列研究的数据。
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.
机构信息
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Center for Quantitative Sciences, Vanderbilt University, Nashville, Tennessee.
出版信息
J Thorac Oncol. 2019 Sep;14(9):1666-1671. doi: 10.1016/j.jtho.2019.06.009. Epub 2019 Jun 20.
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.
简介
MNNG HOS 转化基因（MET）扩增和 MET 外显子 14（METex14）改变会影响对 MET 原癌基因、受体酪氨酸激酶（MET[也称为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）已被用于评估 MET 依赖性。在这里，我们确定了 MET IHC 与 METex14 突变和 MET 扩增的关联。
方法
我们从肺癌突变联盟收集了三机构队列的数据。所有患者均患有转移性肺腺癌且无先前的靶向治疗。使用 SP44 抗体，MET IHC 阳性定义为 H 评分≥200。使用 NGS 或 FISH 检测到 MET 拷贝数倍数变化≥1.8 倍或 MET 与 7 号染色体着丝粒的比值大于 2.2 时，定义为 MET 扩增。
结果
我们对 181 例患者的 MET IHC、MET 扩增和 METex14 突变进行了检测。总体而言，181 例患者中有 71 例（39%）为 MET IHC 阳性，181 例中有 3 例（2%）为 MET 扩增，181 例中有 2 例（1%）携带 METex14 突变。在 MET 扩增的病例中，2 例 FISH 阳性，MET 与 7 号染色体着丝粒的比值分别为 3.1 和 3.3，1 例 NGS 阳性，倍数变化为 4.4x，3 例中有 1 例 MET IHC 阳性。在 71 例 IHC 阳性的病例中，1 例（1%）为 MET 扩增，2 例（3%）为 METex14 突变。在 110 例 MET IHC 阴性的病例中，有 2 例（2%）为 MET 扩增。
结论
在这项研究中，几乎所有 MET IHC 阳性的病例均为 MET 扩增或 METex14 突变阴性。MET IHC 也可能会遗漏 MET 扩增的患者。在这个队列中，MET 扩增的病例数量有限，使得证明 MET IHC 与 MET 扩增之间存在关联具有挑战性。尽管如此，IHC 似乎并不是这些基因组变化的有效筛选方法。FISH 和多重 NGS 面板最适合检测 MET 扩增或 METex14 突变。
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