Annals of Oncology Advance Access originally published online on October 3, 2008
Annals of Oncology 2009 20(2):298-304; doi:10.1093/annonc/mdn635
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lung cancer |
MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients
1 Department of Oncology-Hematology, Istituto Clinico Humanitas IRCCS, Rozzano, Italy
2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston
3 Department of Medicine/Medical Oncology, University of Colorado Cancer Center, Aurora, USA
4 CINECA-Interuniversity Consortium, Bologna, Italy
5 Division of Molecular Pathology, University Hospital, Basel, Switzerland
6 Department of Pathology, Milan University, Rozzano, Italy
* Correspondence to: Dr F. Cappuzzo, Istituto Clinico Humanitas IRCCS, via Manzoni 56, 20089-Rozzano, Italy. Tel: +39-02-82244097; Fax: +39-02-82244590; E-mail: federico.cappuzzo{at}humanitas.it
Background: MET amplification has been detected in 
20% of non-small-cell lung cancer patients (NSCLC) with epidermal growth factor receptor (EGFR) mutations progressing after an initial response to tyrosine kinase inhibitor (TKI) therapy.
Patients and methods: We analyzed MET gene copy number using FISH in two related NSCLC cell lines, one sensitive (HCC827) and one resistant (HCC827 GR6) to gefitinib therapy and in two different NSCLC patient populations: 24 never smokers or EGFR FISH-positive patients treated with gefitinib (ONCOBELL cohort) and 182 surgically resected NSCLC not exposed to anti-EGFR agents.
Results: HCC827 GR6-resistant cell line displayed MET amplification, with a mean MET copy number >12, while sensitive HCC827 cell line had a mean MET copy number of 4. In the ONCOBELL cohort, no patient had gene amplification and MET gene copy number was not associated with outcome to gefitinib therapy. Among the surgically resected patients, MET was amplified in 12 cases (7.3%) and only four (2.4%) had a higher MET copy number than the resistant HCC827 GR6 cell line.
Conclusions: MET gene amplification is a rare event in patients with advanced NSCLC. The development of anti-MET therapeutic strategies should be focused on patients with acquired EGFR-TKI resistance.
Key words: EGFR, gefitinib, MET, non-small cell lung cancer, tyrosine kinase inhibitor
Received for publication March 30, 2008. Revision received August 4, 2008. Accepted for publication August 18, 2008.