Cyclooxygenase isoenzyme-2 and vascular endothelial growth factor are associated with poor prognosis in esophageal adenocarcinoma

J Gastrointest Surg. 2012 May;16(5):956-66. doi: 10.1007/s11605-011-1814-1. Epub 2012 Jan 19.

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.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cohort Studies
  • Confidence Intervals
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Disease-Free Survival
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / surgery
  • Esophagectomy / methods
  • Female
  • Humans
  • Immunohistochemistry
  • Isoenzymes / metabolism*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Survival Analysis
  • Vascular Endothelial Growth Factors / genetics
  • Vascular Endothelial Growth Factors / metabolism*

Substances

  • Biomarkers, Tumor
  • Isoenzymes
  • Vascular Endothelial Growth Factors
  • Cyclooxygenase 2