MET expression and copy number heterogeneity in nonsquamous non-small cell lung cancer (nsNSCLC)
Casadevall Aguilar, David (Universitat Autònoma de Barcelona)
Gimeno, Javier (Hospital del Mar (Barcelona, Catalunya))
Clavé, Sergi (Hospital del Mar (Barcelona, Catalunya))
Taus, Álvaro (Hospital del Mar (Barcelona, Catalunya))
Pijuan, Lara (Hospital del Mar (Barcelona, Catalunya))
Arumí, Miriam (Hospital del Mar (Barcelona, Catalunya))
Lorenzo, Marta (Hospital del Mar (Barcelona, Catalunya))
Menéndez, Silvia (Hospital del Mar (Barcelona, Catalunya))
Cañadas, Israel (Hospital del Mar (Barcelona, Catalunya))
Albanell Mestres, Joan (Universitat Pompeu Fabra)
Serrano, Sergio (Hospital del Mar (Barcelona, Catalunya))
Espinet i Solà, Blanca (Hospital del Mar (Barcelona, Catalunya))
Salido, Marta (Hospital del Mar (Barcelona, Catalunya))
Arriola, Edurne (University of Southampton)

Date:	2015
Abstract:	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. 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. 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). 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.
Grants:	Instituto de Salud Carlos III RD12-0036-0051 Instituto de Salud Carlos III FIS/PI13-00140 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-740
Note:	Altres ajuts: Fundació La Marató de TV3. Ref.666/C/2013
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	C-met ; Immunohistochemistry ; FISH ; Non-small-cell lung cancer ; Heterogeneity
Published in:	Oncotarget, Vol. 6, Núm. 18 (June 2015) , p. 16215-16226, ISSN 1949-2553

DOI: 10.18632/oncotarget.3976
PMID: 26041880

12 p, 2.4 MB

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