Abstract B187: Prevalence of MET copy number variation, MET expression and MET related genomic alterations in all solid tumors pre-screening program. VHIO experience
Authors: Azaro Analía , Argilés Guillem , Alsina María , Elez Elena , Macarulla Teresa , Cruz Cristina , Marino Donatella , Hierro Cinta , Cedres Susana , Navarro Alejandro , Ochoa de Olza María , Braña Irene , Martín-Liberal Juan , Vilaró Marta , Moreno Debora , Martínez Paola , Díaz María , Vivancos Ana , Rodón Jordi , Tabernero Josep , Prudkin Ludmila , Nuciforo Paolo 
Published: May 2016

Abstract
Background: Aberrant MET activation occurs in many types of malignancies and includes protein overexpression, increased gene copy number, amplifications, mutations and deletions. The frequency of genomic alterations in MET varies widely among solid tumors. The criteria for MET amplification and MET overexpression have not been established as well as the relationship between MET amplification, MET expression and additional genomic alterations known to be important in tumor biology. Previous and current phase 1 clinical trials have selected patients without matching MET criterion.
Materials and Methods: From Dec/2012 to Dec/2014, 203 formalin fixed paraffin embedded tumor samples from 197 patients consented to undergo targeted MET analysis. Samples were 117 primary and 86 metastatic tumors. Tumor types included colorectal, gastric, lung, glioblastoma, and breast. Samples were analyzed by fluorescence in situ hybridization (FISH) for MET gene amplification (MET/CEN-7 FISH Zytolight SPEC assay Z-2087, Zytovision), and by immunohistochemistry (IHC) for MET protein expression [Met (D1C2) XP® Rabbit mAb #8198, Cell signaling]. Mutations in key oncogenes were determined using Sequenom (Mass Array) and Amplicon-Mi Seq (Illumina) Cancer Panel.
Results: MET gene copy number variation (&gt;5copies) was found in 11 of 203 samples (5%) and MET gene amplification (based on the definition of MET/CEN-7 ≥2.2) was found in 6 of 203 samples (3%). Eleven (5%) samples had ≥4 or ≤5 copies of MET gene. KRAS mutation was found in 28 of 167 samples (17%) and PIK3CA mutation in 6 of 167 samples (4%). Both mutations were observed in tumor samples with &lt; 4 copies of MET gene. MET IHC positive (≥ 50% positive cells 3+) was found in 11 of 203 samples (5%). Seven of 203 samples (3%) had MET IHC positive (≥ 50% positive cells 3+ and 2+). MET protein expression showed statistical association with MET gene copy number (P&lt;0.001). There was a statistically significant increased expression of MET in metastatic samples compared with primary tumor specimens (P = 0.001).
Conclusion: MET expression is higher in metastatic than primary tumor samples. There is a significant association between MET expression and gene copy number. High MET copy number was more frequent in tumors without KRAS and PIK3CA mutation. Quantitative MET protein expression data will be presented.
MET IHCMET FISH≥ 50% cells 3+≥ 50% cells 3+ and 2+&lt; 50% cells 3+and 2+&lt; 2 copies01 (0.7%)40 (28.2%)2- &lt;4 copies4 (2.8%)3 (2.1%)79 (55.6%)4-5 copies1 (0.7%)1 (0.7%)4 (2.8%)&gt;5 copies5 (3.5%)04 (2.8%)
Citation Format: Analía Azaro, Guillem Argilés, María Alsina, Elena Elez, Teresa Macarulla, Cristina Cruz, Donatella Marino, Cinta Hierro, Susana Cedres, Alejandro Navarro, María Ochoa de Olza, Irene Braña, Juan Martín-Liberal, Marta Vilaró, Debora Moreno, Paola Martínez, María Díaz, Ana Vivancos, Jordi Rodón, Josep Tabernero, Ludmila Prudkin, Paolo Nuciforo. Prevalence of MET copy number variation, MET expression and MET related genomic alterations in all solid tumors pre-screening program. VHIO experience. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B187.