Cyclooxygenase-2 expression in endometrial cancer: correlation with microvessel count and expression of vascular endothelial growth factor and thymidine phosphorylase

Hum Pathol. 2002 Feb;33(2):213-9. doi: 10.1053/hupa.2002.31292.

Abstract

Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing production of angiogenic factors. These mechanisms require clarification in endometrial cancer. COX-2 expression was examined by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) in endometrial cancer, endometrial hyperplasia, and normal endometrium in various phases. We investigated the relationship between COX-2 expression and clinicopathologic variables, microvessel count, and expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). Immunohistochemistry demonstrated COX-2 protein in cancerous epithelial cells but not in stromal cells. COX-2 expression in epithelial cells was significantly greater in endometrial cancer (n = 63) and endometrial hyperplasia (n = 6) than in normal endometrium in any phase (n = 53). Although COX-2 did not correlate with any conventional clinicopathologic factor in patients with endometrial cancer, COX-2 expression was associated with high microvessel count, VEGF expression, and TP expression. By combined analysis of COX-2, VEGF, and TP, tumors with high expression of at least one factor had a significantly higher microvessel count than tumors expressing little of the three factors. We confirmed upregulation of COX-2 mRNA expression by RT-PCR in endometrial cancer (n = 17) compared to normal endometrium (n = 12). COX-2 mRNA expression significantly correlated with VEGF mRNA expression in these tumors. COX-2 is upregulated in endometrial cancer and facilitates tumor growth via angiogenesis produced in associated with VEGF and TP. Specific inhibition of COX-2 may be a useful therapeutic intervention in endometrial cancer.

MeSH terms

  • Cyclooxygenase 2
  • Endometrial Hyperplasia / enzymology
  • Endometrial Neoplasms / enzymology*
  • Endometrial Neoplasms / pathology*
  • Endometrium / enzymology
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / genetics*
  • Epithelial Cells / enzymology
  • Female
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Isoenzymes / analysis
  • Isoenzymes / genetics*
  • Lymphokines / analysis
  • Lymphokines / genetics*
  • Membrane Proteins
  • Microcirculation / pathology*
  • Prostaglandin-Endoperoxide Synthases / analysis
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / enzymology
  • Thymidine Phosphorylase / analysis
  • Thymidine Phosphorylase / genetics*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Isoenzymes
  • Lymphokines
  • Membrane Proteins
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Thymidine Phosphorylase