Prognostic significance of HIF-2α/EPAS1 expression in hepatocellular carcinoma

AIM: To evaluate the prognostic significance of HIF-2 alpha(/EPAS1 expression in hepatocellular carcinoma (HCC). METHODS: Surgical specimens from 315 patients with HCC as well as 196 adjacent noncancerous lesions and 22 cases of normal liver tissue were investigated by immunohistochemistry (IHC) for HIF-2 alpha/EPAS1 using a standard detection system. Correlations with clinicopathological factors, VEGF, microvessel density (MVD), and prognosis were analyzed. RESULTS: Immunoreactivity of HIF-2 alpha(/EPAS1 was positive in 69.5% of HCC, 55.6% of adjacent noncancerous tissue, and 0% of normal liver tissue. And it was significantly correlated with tumor grade, venous invasion, intrahepatic metastasis, necrosis, and capsule infiltration. Correlation analysis of HIF-2 alpha(/EPASI with angiogenic factor VEGF (P < 0.001), and MVD (P = 0.016) was also noted. HIF-2 alpha/EPAS1 protein was less frequently expressed in low MVD cases, whereas a high rate of expression was noted in cases with both medium and high MVD (P = 0.042). By Kaplan-Meier analysis, strong HIF-2 alpha,/EPAS1 staining (> 50% of tumor cells) in HCC correlated with a shortened survival in patients (Cox's regression, P < 0.001, r = 3.699). CONCLUSION: We conclude that HIF-2a/EPAS1 expression may play an important role in tumor progression and prognosis of HCC. Assessment of HIF-2 alpha/EPAS1 expression in HCC may be used as a diagnostic tool and possibly a target in the treatment of HCC. (C) 2007 The WIG Press. All rights reserved.