Expression of cyclooxygenase-2 in human hepatocellular carcinoma: relevance to tumor dedifferentiation

Hepatology. 1999 Mar;29(3):688-96. doi: 10.1002/hep.510290355.


Cyclooxygenase (COX) is a key enzyme in the synthesis of prostanoids. Two isoforms of this enzyme have been identified: COX-1 and COX-2. Recent studies have suggested that COX-2, but not COX-1, may play a role in colorectal tumorigenesis. In the present study, we investigated the expression of COX-2 as well as COX-1 in human hepatocellular carcinoma (HCC) tissues using immunohistochemistry and immunoblotting. Forty-four surgically resected HCC tissues with adjacent nontumorous livers (NTs), involving 17 cases of chronic viral hepatitis and 27 cases of cirrhosis, and 7 surgically resected, histologically normal liver tissues were used. The well-differentiated HCC expressed COX-2 more frequently and strongly than less-differentiated HCC or hepatocytes of NTs. Less-differentiated HCCs expressed less COX-2 than hepatocytes of NTs, which showed scattered, strong COX-2 expression. Histologically normal liver was weakly positive for COX-2. The expression of COX-1 was weaker than that of COX-2 in hepatic neoplastic and non-neoplastic parenchymal cells. An enhanced expression of COX-1 was not observed in well-differentiated HCCs. Immunoblotting also confirmed up-regulation of COX-2, but not COX-1, in well-differentiated HCCs. The present study is the first to demonstrate a high expression of COX-2 in well-differentiated HCC and a low expression in advanced HCC, in contrast to its continuous expression during colorectal carcinogenesis. These findings suggested that COX-2 may play a role in the early stages of hepatocarcinogenesis, but not in the advanced stages, and may consequently be related to HCC dedifferentiation.

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / pathology
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Female
  • Humans
  • Immunohistochemistry
  • Isoenzymes / metabolism*
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / pathology
  • Male
  • Membrane Proteins
  • Middle Aged
  • Prostaglandin-Endoperoxide Synthases / metabolism*


  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases