Author of

• 18606

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  P3.03 - Poster Session with Presenters Present (ID 473)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18623

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    P3.03-017 - Fluorescent in situ Hybridization Analysis of MET Gene Status in Malignant Mesothelioma (ID 5413)

    14:30 - 14:30  |  Author(s): M.C. Franceschini
    • Abstract

    Background:
    Malignant mesothelioma (MM) is an aggressive tumor, with poor prognosis and limited possibility of treatment. MMNG HOS Transforming gene (MET) is a proto-oncogene located in the 7q31 that encodes the high-affinity receptor for hepatocyte growth factor (HGF). MET tyrosine-kinase was recently proposed for a targeted therapy and clinical trials are in progress in many tumors. MET amplification identifies a subgroup of patients potentially able to respond to HGF/MET inhibitors and may represent an element of resistance for anti-EGFR inhibitor therapy. The aim of this study was to evaluate MET amplification and expression in MM.
    
    Methods:
    The protocol of this study was approved by the Liguria Region Ethics Committee (P.R. 207REG2014) and the written informed consent was obtained from all the patients. We analysed 109 MM (67 male; 65 epithelioid, 26 sarcomatoid, 14 biphasic, 2 desmoplastic, 2 papillary). Seventy-nine MM were from a tissue microarray (MS801 and MS 1001, US Biomax Inc, Rockville, MD, USA), 12 cases of formalin-fixed paraffin-embedded tissues were from, IRCCS AOU San Martino-IST (Genova) and 18 tissues from ASL N°5 (La Spezia). MET gene amplification was investigated by FISH using MET/CEP7 probe cocktail (Vysis MET Spectrum Red FISH Probe Kit reagent/Vysis CEP 7 (D7Z1) SpectrumGreen Probe, both reagents from Abbott Molecular, Des Plaines, IL USA). Immunohistochemistry was performed by Anti-c-Met Antibody IHC-plus™ LS-B2812 (LSBio, Seattle, WA).
    
    Results:
    By using the UCCC-scored system we found one epithelioid MET amplification (MET to CEP7 ratio ≥2 or at least 15 copies of MET signals in ≥10% of the tumour cells). In contrast, 8/109 (7.3%) MM (6 epithelioid, 1 sarcomatoid, 1 biphasic) showed high MET polysomy (according to mean ≥4 copies/cells in ≥40% of tumour cells) in a range of 4-10 spots of MET gene in about 60-80% of tumour cells. (Table 1). Immunohistochemistry showed that amplification was associated with moderate expression of MET protein in cytoplasm and membrane of MM cells. In contrast, high gene polisomy resulted always associated with low staining of MET protein.
    
    Conclusion:
    Amplification and high polysomy of MET, associated with c-MET receptor expression may be present in MM. These preliminary observations might represent the basis for designing new clinical trials assessing MET targeting agents in MM. Moreover, the possibility of MET amplification should be considered before starting MM patient treatment with the anti-EGFR targeted inhibitors.