The prognostic significance of vasohibin 1-associated angiogenesis in patients with hepatocellular carcinoma.
Vasohibin 1, an endothelium-derived negative feedback regulator of angiogenesis, is induced by fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor A (VEGF-A). In this study, we retrospectively evaluated immunoreactivity of FGF-2 and VEGF-A as well as microvessel density (MVD) determined by expression of vasohibin 1 and CD34 (MVD-CD34) and correlated the findings with clinical outcomes of 181 patients with hepatocellular carcinoma (HCC). Double immunostaining of an endothelial marker CD34 and vasohibin 1 with Ki-67 was also performed to assess angiogenic activity of endothelial cells in HCC. The ratio of Ki-67-positive endothelial cells in vasohibin 1-positive vessels (22%) was significantly higher than that of CD34-positive vessels (9%, P < .001), suggesting the correlation between vasohibin 1 and neovascularization in endothelial cells of HCC. MVD-CD34 decreased, but the ratio of MVD determined by expression of vasohibin 1 to MVD-CD34 (vasohibin 1/CD34) increased significantly according to histologic grade. Vasohibin 1 was significantly correlated with the status of FGF-2 (P = .007) but not with that of VEGF-A (P = .055). The 10-year overall survival and the 2-year disease-free survival rates of the low vasohibin 1/CD34 group (vasohibin 1/CD34 ≤0.459) were significantly higher than those of the high vasohibin 1/CD34 group (vasohibin 1/CD34 >0.459) (survival, 48% versus 38% and 52% versus 35%; P < .001 and P < .05, respectively). In addition, vasohibin 1/CD34 in HCC patients was an independent marker of poor prognosis, as determined by multivariate analysis (risk ratio, 1.973; 95% confidence interval, 1.049-3.711; P = .035). Vasohibin 1/CD34 could identify the proliferative vessels and could be a useful biomarker for predicting the clinical outcome of HCC patients.
Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan; Department of Pathology, Tohoku University Hospital, Sendai 980-8574, Japan. Electronic address: kehgo@med.tohoku.ac.jp.
Keigo
K
Murakami
Department of Pathology, Tohoku University Hospital, Sendai 980-8574, Japan.
Atsuko
A
Kasajima
Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan.
Naoki
N
Kawagishi
Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan.
Satoshi
S
Sekiguchi
Department of Pathology, Tohoku University Hospital, Sendai 980-8574, Japan.
Fumiyoshi
F
Fujishima
Department of Pathology, Tohoku University Hospital, Sendai 980-8574, Japan.
Mika
M
Watanabe
Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-9575, Japan.
Yasufumi
Y
Sato
Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan.
Noriaki
N
Ohuchi
Department of Pathology, Tohoku University Hospital, Sendai 980-8574, Japan.
Hironobu
H
Sasano
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C493181:VASH1 protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2
Angiogenesis; CD34; Hepatocellular carcinoma; Microvessel density; Vasohibin 1