Expression of cyclooxygenase-2 in advanced stage ovarian serous carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, and survival

Am J Obstet Gynecol. 2005 Mar;192(3):819-25. doi: 10.1016/j.ajog.2004.10.587.

Abstract

Objective: Cyclo-oxygenase-2 seems to be involved at various steps in the processes of tumor progression. The objective of this study was to examine the relationship between cyclo-oxygenase-2 expression and tumor proliferation, apoptosis and angiogenesis in patients with advanced stage high-grade ovarian carcinoma.

Study design: Specimens from 118 patients with high-grade and advanced stage (III, IV) serous ovarian carcinoma were evaluated by immunohistochemistry for cyclo-oxygenase-2, Ki-67, vascular endothelial growth factor, and bcl-2 expression. Tumor microvessel density was assessed with CD34 immunostaining. We investigated the relationships between cyclo-oxygenase-2 expression and clinicopathologic characteristics, tumor angiogenesis (tumor microvessel density and vascular endothelial growth factor expression), and tumor proliferation and apoptosis. The effect of cyclooxygenase-2 expression on patient survival was determined.

Results: There was a significant positive correlation between cyclo-oxygenase-2 expression in tumor cells and markers of tumor proliferation and angiogenesis. In univariate survival analysis, high cyclo-oxygenase-2 and high Ki-67 expression showed a significant impact of on patient survival (P < .001). In multivariate regression analysis, only Ki-67 expression retained its significance as an independent poor prognostic factor (death hazard ratio, 2.0; 95% CI, 1.2-3.3; P < .001).

Conclusion: Expression of cyclo-oxygenase-2 correlates with tumor proliferation and tumor angiogenesis but not with apoptotic markers (bcl-2 expression) in high-grade, advanced-stage serous ovarian carcinoma.

MeSH terms

  • Antigens, CD34 / analysis
  • Apoptosis*
  • Biomarkers, Tumor / analysis*
  • Cell Proliferation*
  • Cyclooxygenase 2
  • Cystadenocarcinoma, Serous / mortality*
  • Cystadenocarcinoma, Serous / pathology*
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Membrane Proteins
  • Neovascularization, Pathologic*
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / pathology*
  • Prostaglandin-Endoperoxide Synthases / analysis*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Antigens, CD34
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases