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

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Xavier MignardMarie Wislez

Abstract

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....Continue Reading

Citations

Jun 10, 2020·Nature Reviews. Clinical Oncology·Robin GuoAlexander Drilon
Jun 14, 2020·Cancer Discovery·Gonzalo RecondoMark M Awad
Jan 27, 2021·Critical Reviews in Oncology/hematology·Fatemeh MoosaviOmidreza Firuzi
May 8, 2021·Expert Review of Anticancer Therapy·Janakiraman Subramanian, Ossama Tawfik

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