Prognostic significance of HIF-2alpha/EPAS1 expression in hepatocellular carcinoma.
OBJECTIVE
To evaluate the prognostic significance of HIF-2alpha/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-2alpha/EPAS1 using a standard detection system. Correlations with clinicopathological factors, VEGF, microvessel density (MVD), and prognosis were analyzed.


RESULTS
Immunoreactivity of HIF-2alpha/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-2alpha/EPAS1 with angiogenic factor VEGF (P<0.001), and MVD (P=0.016) was also noted. HIF-2alpha/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-2alpha/EPAS1 staining (>50% of tumor cells) in HCC correlated with a shortened survival in patients (Cox's regression, P<0.001, r=3.699).


CONCLUSIONS
We conclude that HIF-2alpha/EPAS1 expression may play an important role in tumor progression and prognosis of HCC. Assessment of HIF-2alpha/EPAS1 expression in HCC may be used as a diagnostic tool and possibly a target in the treatment of HCC.
Bangoura
Gassimou
G
Department of General Surgery and Liver Cancer Laboratory, Zhong Nan Hospital, Wuhan University School of Medicine, Wuhan 430071, Hubei Province, China.
Liu
Zhi-Su
ZS
Qian
Qun
Q
Jiang
Cong-Qing
CQ
Yang
Gui-Fan
GF
Jing
Sun
S
D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry; D008113:Liver Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1