c-MET Overexpression as a Poor Predictor of MET Amplifications or Exon 14 Mutations in Lung Sarcomatoid Carcinomas

外显子 荧光原位杂交 免疫组织化学 医学 基因复制 肺癌 病理 突变 拷贝数变化 分子生物学 17号染色体(人) 肉瘤样癌 癌症研究 基因 染色体 内科学 生物 遗传学 基因组
作者
Xavier Mignard,Anne-Marie Ruppert,Martine Antoine,Julie Vasseur,Nicolas Girard,Julien Mazières,Denis Moro-Sibilot,Vincent Fallet,Nathalie Rabbe,F. Thivolet‐Béjui,Isabelle Rouquette,Sylvie Lantuéjoul,A. Cortot,Raphaël Saffroy,J. Cadranel,Antoinette Lemoine,Marie Wislez
出处
期刊:Journal of Thoracic Oncology [Elsevier]
卷期号:13 (12): 1962-1967 被引量:48
标识
DOI:10.1016/j.jtho.2018.08.008
摘要

IntroductionMNNG 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.MethodsTissue 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.ResultsA 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%.ConclusionIHC is not a relevant screening tool for MET abnormalities in LSC.

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