Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver: possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases.
Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) has been reported to be responsible for enhanced tumor growth and angiogenesis in various tumors. However, the relationships between tumor vascularity and COX-2 and iNOS expression have not been evaluated in hepatocellular carcinoma (HCC). In this study, we examined the expression of iNOS and COX-2 and microvessel density (MVD) by immunohistochemical staining in 100 tissue sections collected from HCC patients. iNOS expression was significantly higher in hepatitis C virus (HCV)-positive HCCs (P = 0.011). COX-2 expression was significantly correlated with iNOS expression (P = 0.046) and tumor MVD (P = 0.011) in HCV-positive HCCS: iNOS expression was neither correlated with MVD nor had any influence on patient survival; however, combined negative expression of iNOS and COX-2 had a significant impact on patient survival (P = 0.041 and 0.018, log-rank test for overall and recurrence-free survival rate, respectively). The present findings suggest that combined expression of iNOS and COX-2 may play an important role in prognosis of HCV-positive HCC patients and that this could be partially attributable to modulation of angiogenesis by COX-2.
Rahman
M A
MA
Second Department of Surgery, Shimane Medical University, Izumo 693-8501, Japan. rahman@shimane-med.ac.jp
Dhar
D K
DK
Yamaguchi
E
E
Maruyama
S
S
Sato
T
T
Hayashi
H
H
Ono
T
T
Yamanoi
A
A
Kohno
H
H
Nagasue
N
N
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis; D018952:Antigens, CD34 / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D051546:Cyclooxygenase 2; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000502:physiology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000821:virology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000502:physiology
D000906:Antibodies; D018952:Antigens, CD34; D007527:Isoenzymes; D008565:Membrane Proteins; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases