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 an giogenesis in various tumors. However, the relationships between tumor vasc ularity and COX-2 and iNOS expression have not been evaluated in hepatocell ular 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 significa ntly higher in hepatitis C virus (HCV)-positive HCCs (P = 0.011). COX-2 exp ression was significantly correlated with iNOS expression (P = 0.046) and t umor MVD (P = 0.011) in HCV-positive HCCs, iNOS expression was neither corr elated with MVD nor had any influence on patient survival; however, combine d 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-fr ee survival rate, respectively). The present findings suggest that combined expression of iNOS and COX-2 may play an important role in prognosis of HC V-positive HCC patients and that this could be partially attributable to mo dulation of angiogenesis by COX-2.