Abstract |
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.
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Authors | Keigo Murakami, Atsuko Kasajima, Naoki Kawagishi, Satoshi Sekiguchi, Fumiyoshi Fujishima, Mika Watanabe, Yasufumi Sato, Noriaki Ohuchi, Hironobu Sasano |
Journal | Human pathology
(Hum Pathol)
Vol. 45
Issue 3
Pg. 589-97
(Mar 2014)
ISSN: 1532-8392 [Electronic] United States |
PMID | 24444468
(Publication Type: Journal Article)
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Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
- Biomarkers, Tumor
- Cell Cycle Proteins
- VASH1 protein, human
- Vascular Endothelial Growth Factor A
- Fibroblast Growth Factor 2
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Topics |
- Adult
- Aged
- Biomarkers, Tumor
- Carcinoma, Hepatocellular
(blood supply, metabolism, mortality, pathology)
- Cell Cycle Proteins
(metabolism)
- Disease-Free Survival
- Female
- Fibroblast Growth Factor 2
(metabolism)
- Humans
- Liver Neoplasms
(blood supply, metabolism, mortality, pathology)
- Male
- Middle Aged
- Neovascularization, Pathologic
(metabolism, mortality, pathology)
- Prognosis
- Retrospective Studies
- Survival Analysis
- Vascular Endothelial Growth Factor A
(metabolism)
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