Expression of cyclooxygenase-2 in human hepatocellular carcinoma: relevance to tumor dedifferentiation.
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.
Koga
H
H
Second Department of Medicine, Kurume University Research Center for Innovative Cancer Therapy, Kurume, Japan. hirokoga@med.kurume-u.ac.jp
Sakisaka
S
S
Ohishi
M
M
Kawaguchi
T
T
Taniguchi
E
E
Sasatomi
K
K
Harada
M
M
Kusaba
T
T
Tanaka
M
M
Kimura
R
R
Nakashima
Y
Y
Nakashima
O
O
Kojiro
M
M
Kurohiji
T
T
Sata
M
M
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases