title: Cyclooxygenase isoenzyme-2 and vascular endothelial growth factor are associated with poor prognosis in esophageal adenocarcinoma.
abstract: BACKGROUND
  Cyclooxygenase isoenzyme-2 (COX-2) and vascular endothelial growth factor (VEGF) contribute to angiogenesis and are overexpressed in various malignancies. The aim of the study was to evaluate expression, prognostic value and correlation between COX-2 and VEGF expression in esophageal adenocarcinoma (EAC).
  
  
  METHODS
  Surgical specimens of 154 patients with EAC were used to construct a tissue micro array (TMA). TMA sections were immunohistochemically stained for COX-2 and VEGF and scored on intensity of staining.
  
  
  RESULTS
  Estimated 5-year cancer specific survival was 37%. High COX-2 and VEGF expression was observed in 39 (26.5%) and in 77 (53.8%) tumors, respectively. Both markers were associated with poor cancer specific survival (p = .022 and p = .004, respectively, log rank). No significant correlation was found between VEGF and COX-2 expression (r = 063; p = .455). In multivariate analysis, high COX-2 expression (HR 1.65; 95% CI 1.04-2.61; p = .034) was associated with overall survival. In patients with T3 tumors, COX-2 expression was an independent prognostic factor for cancer specific survival (HR 1.81 95% CI 1.10-2.95; p = .019).
  
  
  CONCLUSIONS
  This is the first study that evaluated the prognostic value and correlation of COX-2 and VEGF expression in a large and homogenous population of patients with EAC. No correlation between COX-2 and VEGF expression was found. Both markers were expressed in EAC and were associated with poor prognosis. The findings support the use of COX-2 and VEGF inhibitors in future clinical studies.
authors.affiliation: Department of Surgery, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
authors.forename: M J D
authors.initials: MJ
authors.lastname: Prins
authors.forename: R J J
authors.initials: RJ
authors.lastname: Verhage
authors.forename: F J W
authors.initials: FJ
authors.lastname: ten Kate
authors.forename: R
authors.initials: R
authors.lastname: van Hillegersberg
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D016001:Confidence Intervals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D016629:Esophagectomy / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D042442:Vascular Endothelial Growth Factors; D051546:Cyclooxygenase 2