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Title: Mesenchyme to epithelial transition protein expression, gene copy number and clinical outcome in a large non-small cell lung cancer surgical cohort.
Austin Authors: Rivalland, Gareth;Mitchell, Paul L R ;Murone, Carmel ;Asadi, Khashayer;Morey, Adrienne L;Starmans, Maud;Boutros, Paul C;Walkiewicz, Marzena;Solomon, Benjamin;Wright, Gavin;Knight, Simon;John, Thomas 
Affiliation: Department of Thoracic Surgery, Austin Health, Heidelberg, Victoria, Australia
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada
Department of Anatomical Pathology, St Vincent's Hospital, Sydney, Australia
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
Research and Education Lead in Lung Cancer, Victorian Comprehensive Cancer Centre, Parkville, Australia
Department of Surgery, University of Melbourne, St Vincent's Hospital, Fitzroy, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Faculty of Medicine, University of Melbourne, Melbourne, Australia
Department of Medical Oncology, Austin Health, Olivia-Newton John Cancer and Wellness Research Centre, Heidelberg, Victoria, Australia
Department of Pathology, Austin Health, Heidelberg, Victoria, Australia
Ontario Institute for Cancer Research, Toronto, Canada
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada
Department of Radiation Oncology (Maastro), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
Department of Medical Biophysics, University of Toronto, Toronto, Canada
Issue Date: Apr-2019
Publication information: Translational lung cancer research 2019; 8(2): 167-175
Abstract: In non-small cell lung cancer (NSCLC), mesenchyme to epithelial transition (MET) protein abundance increases with disease stage and is implicated in resistance to tyrosine kinase inhibitors. To better clarify the impact of MET overexpression on tumor behavior, we investigated a large cohort of patients who underwent curative surgical resection to determine whether MET gene amplification or protein abundance was prognostic. Tissue microarrays (TMAs) were constructed using triplicate 1 mm cores of FFPE primary NSCLC specimens. TMAs underwent immunohistochemical (IHC) staining with the SP44 clone (Ventana) and cores were considered positive if >50% of tumor exhibited 2+ staining. The highest of triplicate values was used. MET gene amplification was detected using either SISH using Ventana's MET DNP probe or FISH using the D7S486/CEP 7 Abbott Probe. DNA was subjected to mutational profiling using Sequenom's LungCarta panel. Data from two institutions comprising 763 patients (516; 68%) male were generated, including 360 stage I, 226 stage II, 160 stage III and 18 resected stage IV. High MET protein expression was detected in 25% (193/763), and was significantly more common in adenocarcinomas than squamous cell carcinoma (P<0.01). MET gene copy number (GCN) correlated with high MET protein expression by IHC (P=0.01). Increased MET protein expression was associated with EGFR and KRAS mutations (P<0.01 for both). Once polysomy was excluded, true MET gene amplification was detected in only 8/763 (1%) of samples. In multivariate analysis, neither MET protein abundance nor GCN were correlated to overall patient survival. MET expression by IHC and GCN amplification was not prognostic in this large Caucasian surgical series. MET's primary role remains as a therapeutic target.
DOI: 10.21037/tlcr.2019.03.11
Journal: Translational lung cancer research
PubMed URL: 31106127
ISSN: 2218-6751
Type: Journal Article
Subjects: Immunohistochemistry
in situ hybridisation
mesenchyme to epithelial transition amplification (MET amplification)
mesenchyme to epithelial transition receptor (MET receptor)
non-small cell lung cancer (NSCLC)
Appears in Collections:Journal articles

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