title: Early miR-223 Upregulation in Gastroesophageal Carcinogenesis.
abstract: OBJECTIVE
  To test miR-223 upregulation during gastric (intestinal-type) and Barrett esophageal carcinogenesis.
  
  
  METHODS
  miR-223 expression was assessed by quantitative reverse transcription polymerase chain reaction in a series of 280 gastroesophageal biopsy samples representative of the whole spectrum of phenotypic changes involved in both carcinogenetic cascades. The results were further validated by in situ hybridization on multiple tissue specimens obtained from six surgically treated gastroesophageal adenocarcinomas. miR-223 expression was also assessed in plasma samples from 30 patients with early stage (ie, stages I and II) gastroesophageal adenocarcinoma and relative controls.
  
  
  RESULTS
  In both gastric and esophageal models, miR-223 expression significantly increased along with the severity of the considered lesions (analysis of variance, P  <   .001). Among atrophic gastritis and long-segment Barrett esophagus samples, miR-223 overexpression was significantly associated with the score of intestinal metaplasia. miR-223 plasma levels were significantly upregulated in patients with cancer compared with controls ( t test, both P  <   .001).
  
  
  CONCLUSIONS
  miR-223 early upregulation observed in tissue samples and its diagnostic value in discriminating patients with early adenocarcinoma by plasma testing provide a solid rationale for further exploring the diagnostic reliability of this microRNA as a novel biomarker in gastroesophageal adenocarcinoma secondary prevention strategies.
authors.affiliation: From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit.
authors.forename: Deborah
authors.initials: D
authors.lastname: Saraggi
authors.affiliation: From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit.
authors.forename: Laura
authors.initials: L
authors.lastname: Balsamo
authors.affiliation: Gastroenterology Unit.
authors.forename: Stefano
authors.initials: S
authors.lastname: Realdon
authors.affiliation: Surgery Unit, Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Surgery Unit, Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castoro
authors.affiliation: From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit.
authors.forename: Irene
authors.initials: I
authors.lastname: Coati
authors.affiliation: From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit.
authors.forename: Roberta
authors.initials: R
authors.lastname: Salmaso
authors.affiliation: Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit.
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
authors.affiliation: From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.affiliation: Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit.|Venetian Institute of Molecular Medicine.
authors.forename: Diletta
authors.initials: D
authors.lastname: Arcidiacono
authors.affiliation: From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit.
authors.forename: Giada
authors.initials: G
authors.lastname: Munari
authors.affiliation: Comprehensive Cancer Center, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gasparini
authors.affiliation: Department of Medicine (DIMED), Geriatrics Division, University of Padua, Padua, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Surgical Pathology Unit, Santa Chiara Hospital, Trento, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchini
authors.affiliation: Gastrointestinal Oncology and Lymphoma, Royal Mardsen Hospital, London and Sutton, UK.|Department of Molecular Pathology, Institute of Cancer Research, London and Sutton, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Valeri
authors.affiliation: From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit.|Veneto Tumour Registry, Padua, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D055088:Early Detection of Cancer / Q000379:methods*; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C525067:MIR223, human
keywords: Barrett carcinogenesis; Gastric adenocarcinoma; Preneoplastic lesions; microRNA