Prevalence and clinical association of MET gene overexpression and amplification in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape project

Lukas Bubendorf*, Urania Dafni, Martin Schobel, Stephen P. Finn, Verena Tischler, Aleksandra Sejda, Antonio Marchetti, Erik Thunnissen, Eric K. Verbeken, Arne Warth, Irene Sansano, Richard Cheney, Ernst Jan M. Speel, Daisuke Nonaka, Kim Monkhorst, Henrik Hager, Miguel Martorell, Spasenija Savic, Keith M. Kerr, Qiang TanZoi Tsourti, Thomas R. Geiger, Roswitha Kammler, Katja Schulze, Ashis Das-Gupta, David Shames, Solange Peters, Rolf A. Stahel, Lungscape Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

36 Citations (Web of Science)

Abstract

Introduction: In a well-defined NSCLC cohort of the ETOP Lungscape program, we explored the epidemiology of IHC MET overexpression and amplification, their inter-correlation, and their association to outcome.

Methods: Resected NSCLC were assessed for MET gene copy number (GCN) and expression using silver in-situ hybridization (SISH) and immunohistochemistry (IHC) on TMAs in a multicenter setting. MET amplification was defined as MET/centromere ratio >= 2 (with average MET GCN >= 4), high MET GCN as CGN >= 5 and MET IHC + as >= 2 + intensity in >= 50% of tumor cells. A total of 182 MET IHC + and EGFR/KRAS WT tumors were analyzed for METex14 skipping mutation.

Results: MET IHC+ was found in 23.8% of 2432 patients, significantly associated with female gender, small tumor size, and adenocarcinoma histology. We observed a high inter-laboratory variability in IHC and SISH analysis. MET amplification prevailed in 4.6% and MET GCN >= 5 in 4.1% of 1572 patients. MET amplification and MET GCN >= 5 were not significantly associated with any tumor characteristics or stage. Both were significantly associated with IHC MET positivity (p <0.001). METex14 skipping mutation prevailed in 5 of 182 (2.7%) MET IHC + WT EGFR/KRAS NSCLC, 4 of which within the 88 adenocarcinomas (4.5%). No association of IHC MET overexpression, SISH MET amplification or high MET GCN was found with OS, RFS or TTR.

Conclusion: MET overexpression is found in 23.8% of surgically resected NSCLC. MET amplification prevails in 4.6% and is associated with MET overexpression. Both have no influence on prognosis. The large inter-laboratory variability in IHC highlights the challenge of MET IHC analysis in routine practice.

Original languageEnglish
Pages (from-to)143-149
Number of pages7
JournalLung Cancer
Volume111
DOIs
Publication statusPublished - Sep 2017

Keywords

  • Non-small cell lung carcinoma
  • IHC MET overexpression
  • SISH MET amplification
  • MET exon14 mutation
  • CELL LUNG-CANCER
  • COPY NUMBER
  • PROTEIN EXPRESSION
  • TARGETING MET
  • IMMUNOHISTOCHEMISTRY
  • MUTATIONS
  • ADENOCARCINOMAS
  • CARCINOMAS
  • INHIBITORS
  • SURVIVAL

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