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MET expression and copy number heterogeneity in nonsquamous non-small cell lung cancer (nsNSCLC).

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dc.contributor.author Casadevall Aguilar, David
dc.contributor.author Gimeno Beltran, Javier
dc.contributor.author Clavé Safont, Sergi
dc.contributor.author Taus García, Álvaro
dc.contributor.author Pijuan Andujar, Lara
dc.contributor.author Arumí de Dios, Miriam
dc.contributor.author Lorenzo Perez, Marta
dc.contributor.author Menendez Romero, Silvia
dc.contributor.author Cañadas Castillo, Israel, 1984-
dc.contributor.author Albanell Mestres, Joan
dc.contributor.author Serrano Figueras, Sergi
dc.contributor.author Espinet Solà, Blanca
dc.contributor.author Salido Galeote, Marta
dc.contributor.author Arriola Aperribay, Edurne
dc.date.accessioned 2015-11-23T09:41:12Z
dc.date.available 2015-11-23T09:41:12Z
dc.date.issued 2015
dc.identifier.citation Casadevall D, Gimeno J, Clavé S, Taus Á, Pijuan L, Arumí M. et al. MET expression and copy number heterogeneity in nonsquamous non-small cell lung cancer (nsNSCLC). Oncotarget. 2015 Jun 30;6(18):16215-26. DOI: 10.18632/oncotarget.3976
dc.identifier.issn 1949-2553
dc.identifier.uri http://hdl.handle.net/10230/25178
dc.description.abstract OBJECTIVE: We aimed to assess MET intratumoral heterogeneity and its potential impact on biomarker-based patient selection as well as potential surrogate biomarkers of MET activation. METHODS: Our study included 120 patients with non-squamous Non-small-cell Lung Cancer (nsNSCLC), of which 47 were incorporated in tissue microarrays (TMA). Four morphologically distinct tumor areas were selected to assess MET heterogeneity. MET positivity by immunohistochemistry (IHC) was defined as an above-median H-score and by +2/+3 staining intensity in >50% of tumor cells (Metmab criteria). MET FISH positivity was defined by MET/CEP7 ratio ≥ 2.0 and/or MET ≥ 5.0. MET staining pattern (cytoplasmic vs. membranous) and mesenchymal markers were investigated as surrogates of MET activation. RESULTS: Median MET H-score was 140 (range 0-400) and 47.8% of patients were MET positive by Metmab criteria. Eight cases (6.8%) were MET FISH positive and showed higher H-scores (p = 0.021). MET positivity by IHC changed in up to 40% of cases among different tumor areas, and MET amplification in 25-50%. Cytoplasmic MET staining and positivity for vimentin predicted poor survival (p = 0.042 and 0.047, respectively). CONCLUSIONS: MET status is highly heterogeneous among different nsNSCLC tumor areas, hindering adequate patient selection for MET-targeted therapies. MET cytoplasmic staining and vimentin might represent surrogate markers for MET activation.
dc.description.sponsorship This work was supported by RD12/0036/0051 /FEDER, PI13/00140/FEDER, a grant from Fundacio Marato de TV3. Ref.666/C/2013 and 2014 SGR 740. the “Xarxa de Bancs de tumors sponsored by Pla Director d’Oncologia de Catalunya (XBTC).” JA is recipient of intensification programme ISCIII.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Impact Journals
dc.relation.ispartof Oncotarget. 2015 Jun 30;6(18):16215-26
dc.rights Copyright @ 2008-2015 Impact Journals. All site content, except where otherwise noted, is licensed under a http://creativecommons.org/licenses/by/3.0/
dc.rights.uri http://creativecommons.org/licenses/by/3.0/
dc.subject.other Pulmons -- Càncer
dc.title MET expression and copy number heterogeneity in nonsquamous non-small cell lung cancer (nsNSCLC).
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.3976
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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