Cyclooxygenase-2 mRNA is up-regulated in cirrhotic or chronic hepatitis liver adjacent to hepatocellular carcinoma

J Gastroenterol Hepatol. 2002 Oct;17(10):1110-6. doi: 10.1046/j.1440-1746.2002.02836.x.


Background and aim: Hepatocellular carcinoma (HCC) is unique in that its carcinogenesis is related to inflammatory changes and regenerative activities in the background liver. Although there are some data on cyclooxygenase (COX)-2 expression in HCC by immunohistochemical studies, little is known about the possible role of COX-2 in inducing hepatitis and/or carcinoma. To elucidate whether COX-2 is involved in a part of these processes, we attempted to examine COX-2 mRNA both in the adjacent non-tumoral liver and in HCC.

Methods: Twenty-two matched sets of adjacent liver and HCC specimens were analyzed for COX-2 mRNA expression using a real-time quantitative reverse transcription polymerase chain reaction. Cyclooxygenase-2 protein expression was also determined by immunohistochemistry.

Results: Cyclooxygenase-2 mRNA expression was significantly higher in the adjacent liver than in HCC (P = 0.016). Cyclooxygenase-2 mRNA expression in adjacent liver tissues was positively correlated with the modified histological activity index scores (r = 0.575, P = 0.006), the serum alanine aminotransferase levels (r = 0.536, P = 0.010), and the Ki-67 labeling indices (r = 0.698, P = 0.001). In contrast, COX-2 mRNA expression in HCC was not correlated with any of the clinicopathological features.

Conclusions: Cyclooxygenase-2 is expressed at higher levels in the adjacent liver than in HCC, and it may be associated with high levels of necroinflammation and regeneration in the background liver. Conversely, COX-2 may have a lesser role in the progression of HCC.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / analysis
  • Carcinoma, Hepatocellular / enzymology*
  • Cyclooxygenase 2
  • Female
  • Hepatitis, Chronic / enzymology
  • Humans
  • Immunohistochemistry
  • Isoenzymes / metabolism*
  • Liver Cirrhosis / enzymology
  • Liver Neoplasms / enzymology*
  • Male
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Isoenzymes
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Alanine Transaminase