title: Molecular determinants in targeted therapy for esophageal adenocarcinoma.
abstract: OBJECTIVE
  Cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) are useful biological determinants in targeted therapy for esophageal adenocarcinoma.
  
  
  METHODS
  Prospective analysis.
  
  
  METHODS
  University tertiary referral center.
  
  
  METHODS
  Sixteen patients with squamous mucosa and normal results of a pH study without mucosal injury (control group), 15 with Barrett esophagus (metaplasia group), and 44 with adenocarcinoma (carcinoma group).
  
  
  METHODS
  Biopsy specimens were obtained 3 cm above the gastroesophageal junction. Dysplastic tissue was additionally isolated from 9 of the patients in the carcinoma group. After laser-capture microdissection, quantitative real-time polymerase chain reaction was used to measure gene expression across the spectrum of the metaplasia-dysplasia-carcinoma sequence.
  
  
  METHODS
  Expression of COX-2, VEGF, and EGFR in each patient group.
  
  
  RESULTS
  Expression of both COX-2 and VEGF was significantly up-regulated in patients with metaplasia, dysplasia, and cancer compared with controls (P<.01). Expression levels of both were significantly higher in cancer than in the metaplasia group (P<.05) and increased sequentially from metaplasia to dysplasia to cancer. Expression of VEGF was significantly higher in the dysplastic tissue than in nondysplastic Barrett epithelium (P<.05). No change in expression levels of EGFR was seen in the histologic progression to esophageal adenocarcinoma.
  
  
  CONCLUSIONS
  Gene expression data suggest that pharmacologic inhibition of COX-2 and VEGF may be useful adjuncts in targeted therapy for esophageal adenocarcinoma.
authors.affiliation: Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vallböhmer
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Peters
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kuramochi
authors.forename: Daniel
authors.initials: D
authors.lastname: Oh
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shimizu
authors.forename: Steven R
authors.initials: SR
authors.lastname: DeMeester
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hagen
authors.forename: Parakrama T
authors.initials: PT
authors.lastname: Chandrasoma
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Danenberg
authors.forename: Peter V
authors.initials: PV
authors.lastname: Danenberg
authors.forename: Tom R
authors.initials: TR
authors.lastname: DeMeester
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D012334:RNA, Neoplasm / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D066246:ErbB Receptors