title: What is the clinical significance of stromal angiogenesis in Barrett's esophagus?
abstract: BACKGROUND
  Enriched blood vessels occur in the stroma of Barrett's esophagus and are related to the ease of tumor invasion in the early stage of the cancer. Hypoxia-inducible factor (HIF) is closely related with angiogenesis through expression of vascular endothelial growth factor. The aim of the present study was to determine the predictors for angiogenesis in Barrett's esophagus and evaluate their clinical significance.
  
  
  METHODS
  Between December 2003 and May 2004, 209 patients with endoscopically and histologically proven Barrett's esophagus were enrolled. Before endoscopic examination, all participants answered structured questionnaires for gastroesophageal reflux symptoms and drug usage. HIF-1alpha and COX-2 protein expressions, cellular proliferation, and apoptosis were investigated immunohistochemically in biopsy samples taken from the esophagus of each patient. The degree of angiogenesis was determined by CD34 immunostaining analysis. Predictors for angiogenesis were evaluated with multivariate logistic regression analysis.
  
  
  RESULTS
  Sixty (28.7%) of the 209 enrolled patients with Barrett's esophagus had a high CD34 score. Factors proven as positive predictors for a high CD34 score were presence of gastroesophageal reflux symptoms, reflux esophagitis, COX-2 protein expression, and the proliferating cell nuclear antigen (PCNA) index. Administration of proton-pump inhibitors and HIF-1alpha protein expression were not predictors.
  
  
  CONCLUSIONS
  Reflux esophagitis and gastroesophageal reflux symptoms were positive predictors for enriched angiogenesis in the stromal portion of Barrett's esophagus, which has malignant potential because the epithelial cells express COX-2 and have accelerated cellular proliferation.
authors.affiliation: Department of Gastroenterology and Hepatology, Shimane University, School of Medicine, Izumo-shi, Shimane Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Moriyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Amano
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mishima
authors.forename: Koichi
authors.initials: K
authors.lastname: Okita
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yuki
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishimura
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000032:analysis; D004942:Esophagitis, Peptic / Q000473:pathology / Q000503:physiopathology; D004945:Esophagoscopy; D005260:Female; D005764:Gastroesophageal Reflux / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D016017:Odds Ratio; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology*
chemical_list: D018952:Antigens, CD34; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018809:Proliferating Cell Nuclear Antigen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human