1313P - De novo MET overexpression coexisting with oncogenic drivers in advanced non-small-cell lung cancer

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 Na Lou
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors N.N. Lou1, J. Yang2, X. Zhang2, H. Chen3, Y. Wu4
  • 1Division Of Pulmonary Oncology,cancer Center, Guangdong Lung Cancer Institute, 510080 - GUANGZHOU/CN
  • 2Division Of Pulmonary Oncology, Guangdong Lung Cancer Institute, 510080 - Guangzhou/CN
  • 3Guangdong General Hospital, Guangdong Academy Of Medical Sciences, Guangdong Lung Cancer Institute,, Guangdong/CN
  • 4Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN



There were many driver genes in non-small-cell lung cancer (NSCLC), such as EGFR and ALK. De novo MET amplification coexisting with EGFR mutation is recognized as intrinsic resistance to EGFR tyrosine kinase inhibitors (EGFR TKIs) in patients with advanced NSCLC. We investigate the frequency of de novo MET overexpression coexisting with other oncogenic drivers and the response to oncogenic inhibitors in advanced NSCLC patients with such co-alterations.


We screened 195 consecutive patients with advanced NSCLC for the presence of de novo MET overexpression by immunohistochemical (IHC), in which ≥50% tumor cells with moderate to high intensity staining were defined as MET positive, and MET amplification by fluorescence in situ hybridization (FISH). Meanwhile, EGFR and KRAS mutations were detected by DNA sequencing, and ALK rearrangements were also detected by FISH.


The frequency of de novo MET overexpression was 32.8% (64/195) in advanced NSCLC. The overall frequency was 36.0% (23/64) for de novo MET overexpression coexisting with EGFR mutations (n = 14), ALK rearrangements (n = 6) and KRAS mutations (n = 3). Seven patients with concurrent de novo MET overexpression and EGFR mutations were treated with first-line EGFR-TKIs (gefitinib or icotinib), with the response rate of 71.4% (5/7). Among them, one developed intrinsic resistance to icotinib, but achieved partial response after taking third-line crizotinib. One patient had primary resistance to first-line crizotinib. Five patients with concomitant de novo MET overexpression and ALK rearrangements were treated with crizotinib, with the response rate of 80% (4/5). The frequency of MET amplification was 13.6% (3/22) in patients with de novo MET overexpression. Among 2 with concurrent MET amplification and EGFR mutations, one responded to first-line gefitinib, but the other had stable disease. Dramatic response was observed in one with concomitant MET amplification and KRAS mutations, when treated with crizotinib.


De novo MET overexpression or MET amplification could coexist with other oncogenic drivers in a small subgroup of NSCLC. Advanced NSCLC with such co-alterations could have diverse responses to EGFR-TKIs and crizotinib.


All authors have declared no conflicts of interest.