Cyclooxygenase-2 mRNA is up-regulated in cirrhotic or chronic hepatitis liver adjacent to hepatocellular carcinoma.
OBJECTIVE
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.
Morinaga
Soichiro
S
Department of Surgery, Yokohama City Kowan Hospital, Yokohama, Japan. ks067682@city.yokohama.jp
Yamamoto
Yuji
Y
Noguchi
Yoshikazu
Y
Imada
Toshio
T
Rino
Yasushi
Y
Akaike
Makoto
M
Sugimasa
Yukio
Y
Takemiya
Shoji
S
Kameda
Yoichi
Y
Takanashi
Yoshinori
Y
D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D051546:Cyclooxygenase 2; D005260:Female; D006521:Hepatitis, Chronic / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000410:Alanine Transaminase