Title |
MET Amplification Status in Therapy-Naïve Adeno- and Squamous Cell Carcinomas of the Lung
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Published in |
Clinical Cancer Research, February 2015
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DOI | 10.1158/1078-0432.ccr-14-0450 |
Pubmed ID | |
Authors |
Hans-Ulrich Schildhaus, Anne M. Schultheis, Josef Rüschoff, Elke Binot, Sabine Merkelbach-Bruse, Jana Fassunke, Wolfgang Schulte, Yon-Dschun Ko, Andreas Schlesinger, Marc Bos, Masyar Gardizi, Walburga Engel-Riedel, Michael Brockmann, Monika Serke, Ulrich Gerigk, Khosro Hekmat, Konrad F. Frank, Marcel Reiser, Holger Schulz, Stefan Krüger, Erich Stoelben, Thomas Zander, Jürgen Wolf, Reinhard Buettner |
Abstract |
Purpose: MET is a potential therapeutic target in lung cancer and both MET tyrosine kinase inhibitors and monoclonal antibodies have entered clinical trials. MET signaling can be activated by various mechanisms including gene amplification. In this study we aimed to investigate MET amplification status in adeno- and squamous cell carcinomas of the lung. We propose clearly defined amplification scores and provide epidemiologic data on MET amplification in lung cancer. Experimental design: We evaluated the prevalence of increased MET gene copy numbers in 693 treatment-naïve cancers by fluorescence in situ hybridization, defined clear cut-off criteria, and correlated FISH results to MET immunohistochemistry. Results: Two thirds (67%) of lung cancers do not have gains in MET gene copy numbers whereas 3% show a clear-cut high-level amplification (MET/centromer7 ratio ≥2.0 or average gene copy number per nucleus ≥6.0 or ≥10% of tumor cells containing ≥15 MET copies). The remaining cases can be subdivided into intermediate (6%) and low level gains (24%). Importantly, MET amplifications occur at equal frequencies in squamous and adenocarcinomas without or with EGFR or KRAS mutations. Conclusion: MET amplification is not a mutually exclusive genetic event in therapy-naïve NSCLC. Our data suggest that it might be useful to determine MET amplification a) before EGFR inhibitor treatment to identify possible primary resistance to anti-EGFR treatment, and b) to select cases that harbor KRAS mutations additionally to MET amplification and, thus, may not benefit from MET inhibition. Furthermore, our study provides comprehensive epidemiologic data for upcoming trials with various MET inhibitors. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Italy | 1 | 25% |
Spain | 1 | 25% |
Germany | 1 | 25% |
Unknown | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Practitioners (doctors, other healthcare professionals) | 2 | 50% |
Members of the public | 2 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 1 | 1% |
Unknown | 67 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 15 | 22% |
Other | 9 | 13% |
Student > Ph. D. Student | 8 | 12% |
Student > Master | 7 | 10% |
Student > Bachelor | 5 | 7% |
Other | 9 | 13% |
Unknown | 15 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 22 | 32% |
Biochemistry, Genetics and Molecular Biology | 11 | 16% |
Agricultural and Biological Sciences | 6 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
Chemistry | 2 | 3% |
Other | 6 | 9% |
Unknown | 18 | 26% |