Sorbonne University, GRC n°04, Theranoscan, F-75252, Paris, France.
Sorbonne University, GRC n°04, Theranoscan, F-75252, Paris, France; AP-HP, GH HUEP, Tenon Hospital, Chest Department and Thoracic Oncology, F-75970, Paris, France.
J Thorac Oncol. 2018 Dec;13(12):1962-1967. doi: 10.1016/j.jtho.2018.08.008. Epub 2018 Aug 24.
MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities.
Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms.
A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%.
IHC is not a relevant screening tool for MET abnormalities in LSC.
MNNG HOS 转化基因（MET）异常，如扩增和外显子 14 突变，可能对靶向治疗有反应。它们在肺肉瘤样癌（LSC）中很常见，必须尽可能高效地诊断。理论上，免疫组织化学（IHC）检测 c-MET 过表达可能成为 MET 异常的有效筛查试验。
从四个肿瘤中心连续的 LSC 切除患者中获得组织样本。使用 SP44 抗体（Ventana，Tucson，Arizona）进行 IHC，并使用 MetMab 评分和 H 评分进行评估。使用 Zytovision（Clinisciences，Nanterre，法国）的双色探针套进行荧光原位杂交。当 MET 基因拷贝数为 5 或更高，且 MET 基因拷贝数与 7 号染色体数的比值大于 2 时，诊断为真正的 MET 扩增。在常规的分子检测中，通过遗传平台检测到所有 MET 外显子 14 改变，包括影响剪接供体和受体位点内剪接的改变。
共纳入 81 例 LSC。14 例（17%）使用 MetMab 评分和 15 例（18.5%）使用 H 评分显示 IHC 阳性。6 例肿瘤（8.5%）检测到 MET 扩增，5 例（6%）检测到 MET 外显子 14 突变。发现 IHC 与荧光原位杂交之间存在弱正相关（r=0.27，p=0.0001）。IHC 检测 MET 扩增的敏感性为 50%，特异性为 83%，阳性预测值为 21.4%，阴性预测值为 94.7%。IHC 检测 MET 外显子 14 突变的敏感性为 20%，特异性为 83%，阳性预测值为 7%，阴性预测值为 94%。
IHC 不是 LSC 中 MET 异常的相关筛查工具。
Zotero 插件