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

Casadevall Aguilar, David; Gimeno Beltran, Javier; Clavé Safont, Sergi; Taus García, Álvaro; Pijuan Andujar, Lara; Arumí de Dios, Miriam; Lorenzo Perez, Marta; Menendez Romero, Silvia; Cañadas Castillo, Israel, 1984-; Albanell Mestres, Joan; Serrano Figueras, Sergi; Espinet Solà, Blanca; Salido Galeote, Marta; Arriola Aperribay, Edurne

doi:http://dx.doi.org/10.18632/oncotarget.3976

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

Llicència

Citació

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

Resum

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.