title: Overexpression of CMET is associated with signal transducer and activator of transcription 3 activation and diminished prognosis in oesophageal adenocarcinoma but not in squamous cell carcinoma.
abstract: BACKGROUND
  Inhibition of cMet is a promising therapeutic approach in human cancer, but few data in oesophageal cancer exist.
  
  
  METHODS
  Expression of mesenchymal-epithelial transition factor (cMet), epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN) were investigated immunohistochemically in 246 oesophageal carcinomas (128 adenocarcinomas (AC); 118 squamous cell carcinomas (SCC)) and corresponding metastases in a subset of AC (n=42). Data on phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and HER2 expression and on lymphovascular invasion (LVI) of tumour cells were available from previous studies.
  
  
  RESULTS
  Overexpression of cMet was seen in 44 (34.4%) of AC, and nine (7.6%) of SCC (p<0.001, Chi square test). In AC but not in SCC, cMet expression correlated with EGFR expression (p<0.001, Chi square test), pSTAT3 expression (p=0.01, Chi square tests) and LVI of tumour cells (p<0.001, Chi square test). Overexpression of cMet was associated with shorter disease free, disease specific and overall survival of AC patients (p<0.05, Cox regression, respectively). All cMet positive ACs in which metastases were investigated had also cMet positive lymph node and distant metastases, but 25% of cMet negative primary tumours showed cMet positive lymph node and 33% distant metastases.
  
  
  CONCLUSIONS
  CMet plays no relevant role in most oesophageal SCC. In contrast, cMet overexpression seems to be a key oncogene in about 35% of oesophageal AC, representing a highly promising therapeutic target and prognostic factor.
authors.affiliation: Department of Pathology, Medical University of Vienna, A-1090 Vienna, Austria; Comprehensive Cancer Center Vienna Gastroesophageal Cancers Unit (CCC-GET), Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Mesteri
authors.affiliation: Comprehensive Cancer Center Vienna Gastroesophageal Cancers Unit (CCC-GET), Medical University of Vienna, A-1090 Vienna, Austria; Department of Surgery, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Schoppmann
authors.affiliation: Comprehensive Cancer Center Vienna Gastroesophageal Cancers Unit (CCC-GET), Medical University of Vienna, A-1090 Vienna, Austria; Department of Internal Medicine I, Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.affiliation: Department of Pathology, Medical University of Vienna, A-1090 Vienna, Austria; Comprehensive Cancer Center Vienna Gastroesophageal Cancers Unit (CCC-GET), Medical University of Vienna, A-1090 Vienna, Austria. Electronic address: peter.birner@meduniwien.ac.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D016019:Survival Analysis; D015533:Transcriptional Activation
chemical_list: D066246:ErbB Receptors; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D050796:STAT3 Transcription Factor; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human
keywords: C-Met; MET; Oesophageal cancer; Prognosis; Survival; cMet