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

Xavier Mignard1, Anne-Marie Ruppert2, Martine Antoine3

  • 1Sorbonne University, GRC n°04, Theranoscan, F-75252, Paris, France.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
|August 28, 2018
PubMed
Abstract

Insights

Immunohistochemistry (IHC) is not a reliable screening tool for detecting MNNG HOS transforming gene (MET) abnormalities in lung sarcomatoid carcinomas (LSCs). This study found IHC had low sensitivity and predictive values for identifying MET amplification and exon 14 mutations.

Area of Science:

  • Oncology
  • Molecular Pathology
  • Genetics

Background:

  • MNNG HOS transforming gene (MET) abnormalities, including amplification and exon 14 mutations, are potential targets for therapy in lung sarcomatoid carcinomas (LSCs).
  • Efficient diagnosis of MET abnormalities is crucial for timely treatment initiation in LSC patients.
  • Immunohistochemistry (IHC) for c-MET overexpression was hypothesized as a potential screening method for MET alterations.

Purpose of the Study:

  • To evaluate the efficacy of immunohistochemistry (IHC) as a screening tool for detecting MET abnormalities (amplification and exon 14 mutations) in lung sarcomatoid carcinomas (LSCs).

Main Methods:

  • Tissue samples from 81 resected LSCs were analyzed using IHC (MetMab score and H-score) and fluorescence in situ hybridization (FISH) for MET amplification.
  • Routine molecular testing was employed to detect MET exon 14 alterations.
  • Correlation between IHC results and genetic testing (FISH and molecular analysis) was assessed.

Main Results:

  • IHC detected c-MET overexpression in 17-18.5% of LSCs, while MET amplification was found in 8.5% and MET exon 14 mutations in 6%.
  • A weak positive correlation (r=0.27) was observed between IHC and FISH results.
  • IHC demonstrated low sensitivity (50% for amplification, 20% for exon 14 mutations) and low positive predictive values (21.4% for amplification, 7% for exon 14 mutations).

Conclusions:

  • Immunohistochemistry (IHC) is not a relevant or effective screening tool for identifying MET abnormalities in lung sarcomatoid carcinomas (LSCs).
  • The low sensitivity and predictive values indicate that IHC alone is insufficient for guiding targeted therapy decisions in LSCs based on MET status.
Keywords:
AmplificationExon 14 mutationsImmunohistochemistryLung sarcomatoid carcinomaMET

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