1316P - Genetic variability and clinical presentation of patients with non-small cell lung cancer (NSCLC) harboring MET-amplifications

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Pathology/Molecular Biology
Translational Research
Non-small-cell lung cancer
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter Anna Eisert
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors A.K. Eisert1, M. Scheffler2, S. Michels2, A. Schultheis3, K. König4, S. Merkelbach-Bruse5, M. Serke6, Y. Ko7, U. Gerigk8, T. Geist9, L.C. Heukamp4, R. Büttner4, J. Wolf2
  • 1Lung Cancer Group Cologne, University Hospital Cologne, 50924 - Cologne/DE
  • 2Lung Cancer Group Cologne, University Hospital Cologne, Cologne/DE
  • 3Institute Of Pathology, University Hospital Cologne, 50937 - Cologne/DE
  • 4Institute Of Pathology, University Hospital Cologne, Cologne/DE
  • 5Institute Of Pathology, University of Cologne, 50924 - Cologne/DE
  • 6Thoracic Oncology, Hemer Lung Clinic, Hemer/DE
  • 7Department Of Oncology, Johanniter Hospital Bonn, Bonn/DE
  • 8Department Of Thoracic Surgery, Malteser Hospital Bonn, Cologne/DE
  • 9Pneumonology, Schwerpunktpraxis für Lungen- und Bronchialheilkunde, Duesseldorf/DE



cMET (MNNG HOS Transforming gene) is a proto-oncogene encoding the hepatocyte growth factor receptor (HGFR) with HGF as the only known ligand. Whereas the role of cMET mutations in NSCLC patients remains debated controversively, amplification of cMET is considered as one of the molecular resistance mechanisms in EGFR-mutated NSCLCs treated with 1st or 2nd generation EGFR-TKIs. Further, at least for high-level amplifications, these aberrations might be a possible target for cMET-targeted therapy also in EGFR-wt patients. Nevertheless, much is unknown about the contribution and the impact of cMET amplifications regarding their prognostic or predictive value.


Beside the screening of rebiopsied EGFR-TKI-resistant patients, cMET amplification status as assessed by fluorescence in-situ hybridization (FISH) was also analyzed in therapy-naïve patients. A cohort of 588 patients was analyzed using FISH and next-generation sequencing (NGS). The amplifications were categorized as low-level, intermediate, and high-level amplifications.


171 patients with cMET amplification were identified, whereof 11 (6.4%) had a high-level amplification. cMET amplifications cooccured with a large spectrum of other driver mutations (EGFR, KRAS, HER2, STK11, NRAS, BRAF) or amplifications (FGFR1) in both therapy-naïve and treated patients, and smoking status represented the known associations (i. e., low smoking association in patients with EGFR mutations, high association in patients with KRAS and NRAS mutations). The amplifications occurred in both adenocarcinoma and squamous cell carcinoma. Preliminary data suggest that low-level amplifications beside EGFR mutations in therapy-naïve patients do not alter the predictive value of the EGFR mutation.


The preliminary data suggests a higher prevalence of cMET amplifications in a broad spectrum on NSCLC patients. Furthermore, cMET amplifications are not exclusive for EGFR-mutated patients with acquired resistance to EGFR-directed therapy. Preliminary data suggest that low-level amplification does not lead to EGFR-TKI resistance.


All authors have declared no conflicts of interest.