Tumor cyclooxygenase-2 levels correlate with tumor invasiveness in human hepatocellular carcinoma

World J Gastroenterol. 2005 Apr 7;11(13):1896-902. doi: 10.3748/wjg.v11.i13.1896.


Aim: Recent studies suggested that cyclooxygenase-2 (COX-2) enhances tumor angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Although COX-2 expression has been demonstrated in hepatocellular carcinoma (HCC), the significance of COX-2 in progression of HCC remains unclear. This study evaluated the clinico-pathological correlation of COX-2 level and its relationship with VEGF level in HCC.

Methods: Fresh tumor tissues were obtained from 100 patients who underwent resection of HCC. COX-2 protein expression was examined by immunohistochemistry, and quantitatively by an enzyme immunometric assay (EIA) of tumor cytosolic COX-2 levels. Tumor cytosolic VEGF levels were measured by an ELISA.

Results: Immunostaining showed expression of COX-2 in tumor cells. Tumor cytosolic COX-2 levels correlated with VEGF levels (r = 0.469, P<0.001). Correlation with clinicopathological features showed significantly higher tumor cytosolic COX-2 levels in the presence of multiple tumors (P = 0.027), venous invasion (P = 0.030), microsatellite lesions (P = 0.037) and advanced tumor stage (P = 0.008). Higher tumor cytosolic COX-2 levels were associated with worse patient survival.

Conclusion: This study shows that elevated tumor COX-2 levels correlate with elevated VEGF levels and invasiveness in HCC, suggesting that COX-2 plays a significant role in the progression of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cyclooxygenase 2
  • Cytosol / enzymology
  • Female
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Male
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism


  • Biomarkers, Tumor
  • Membrane Proteins
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases