Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue

Hum Pathol. 2004 Apr;35(4):488-95. doi: 10.1016/j.humpath.2003.10.025.


In vitro studies suggest that cyclooxygenase-2 (COX-2) induces angiogenesis by stimulating angiogenic growth factors while inhibiting apoptosis in cancer cell lines. A series of 107 gastric adenocarcinoma cases that had undergone gastrectomy was studied to determine the correlation between COX-2 expression, angiogenesis, and apoptosis in human gastric cancer tissue. COX-2, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and Bcl-2 were stained by single and dual immunoassaying methods. Microvessel density was determined by immunostaining for CD34. Apoptosis was evaluated with the TUNEL assay. COX-2 expression was positive exclusively in cancer cells in 46 cases (43%). COX-2 expression significantly correlated with VEGF and PDGF expression. Dual staining for COX-2 and VEGF showed that colocalization of these proteins was most frequent at the advancing edge of cancer cells. Microvessel density was higher in COX-2-and VEGF-positive cases than in COX-2- and VEGF-negative cases. In addition, COX-2 expression correlated with Bcl-2 expression. The apoptotic index was lower in COX-2-positive cancer cells than in COX-2-negative cases. Multivariate analysis revealed that coexpression of COX-2 and VEGF, age, lymph node status, and serosal invasion were independent prognostic factors for overall survival in gastric cancer patients. Therefore, these data suggest that COX-2 contributes to gastric cancer development by promoting angiogenesis and inhibiting apoptosis.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antigens, CD34 / metabolism
  • Apoptosis / physiology*
  • Cyclooxygenase 2
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Isoenzymes / biosynthesis*
  • Lymphatic Metastasis / pathology
  • Male
  • Membrane Proteins
  • Microscopy, Confocal
  • Middle Aged
  • Neovascularization, Pathologic / metabolism*
  • Platelet-Derived Growth Factor / metabolism
  • Prognosis
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Risk Factors
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / metabolism


  • Antigens, CD34
  • Isoenzymes
  • Membrane Proteins
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-bcl-2
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases