title: Alterations of MET Gene Copy Number and Protein Expression in Primary Non-Small-Cell Lung Cancer and Corresponding Nodal Metastases.
abstract: BACKGROUND
  Mesenchymal epithelial transition factor (MET) is a promising therapeutic target in non-small-cell lung cancer (NSCLC) but there are limited data about MET alterations in treatment-naive NSCLC and whether or not these changes are consistent between primary tumors and metastases. We aimed to investigate concordance, clinicopathological correlations, and prognostic value of MET alterations in primary NSCLC and corresponding nodal metastases.
  
  
  METHODS
  MET gene copy number (GCN) status was evaluated using fluorescent in situ hybridization (FISH) and MET protein expression using immunohistochemistry (IHC) in tissue microarray sections from a retrospective cohort of 300 surgically resected NSCLCs including 93 cases with nodal metastases.
  
  
  RESULTS
  Primary NSCLCs were MET IHC positive in 28 (10.3%) of cases and MET FISH positive (high polysomy or amplification) in 22 (8.1%) but only 1 (0.4%) showed amplification. In metastases, high MET GCN (18.3%) and protein expression (21.3%) was more frequent compared with primary tumors. The status of MET in lymph nodes significantly correlated with MET status in the corresponding primary tumors. Squamous cell carcinomas showed lower MET overexpression compared with nonsquamous tumors but there were no other associations with clinicopathological characteristics. Patients with tumors that were either MET FISH positive or IHC positive had a significantly better overall survival in univariate and multivariate analyses.
  
  
  CONCLUSIONS
  Alterations of MET are more commonly seen in nodal metastases than primary tumors and this might have implications for their utility as predictive biomarkers to select patients for MET inhibition. MET overexpression and MET high polysomy occur in a low proportion of primary NSCLCs and is associated with a good prognosis.
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors.forename: Thang N
authors.initials: TN
authors.lastname: Tran
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Selinger
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; School of Medicine, University of Western Sydney, New South Wales, Australia; St Vincent's Clinical School, University of New South Wales, New South Wales, Australia.
authors.forename: Maija R J
authors.initials: MR
authors.lastname: Kohonen-Corish
authors.affiliation: Sydney Cardiothoracic Surgeons, Royal Prince Alfred Medical Centre, New South Wales, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: McCaughan
authors.affiliation: Sydney Cardiothoracic Surgeons, Royal Prince Alfred Medical Centre, New South Wales, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Kennedy
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, New South Wales, Australia.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: O'Toole
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; School of Medicine, University of Western Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, New South Wales, Australia. Electronic address: Wendy.Cooper@sswahs.nsw.gov.au.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Cooper
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met
keywords: Biomarker; Fluorescent in situ hybridization; Hepatocyte growth factor receptor; Immunohistochemistry; Prognosis