Expression pattern of angiogenic factors and prognosis after hepatic resection in hepatocellular carcinoma: importance of angiopoietin-2 and hypoxia-induced factor-1 alpha. |
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Authors: | Hiroshi Wada Hiroaki Nagano Hirofumi Yamamoto Yubo Yang Motoi Kondo Hideo Ota Masato Nakamura Shinichi Yoshioka Hitoshi Kato Bazarragchaa Damdinsuren Di Tang Sigeru Marubashi Atsushi Miyamoto Yutaka Takeda Koji Umeshita Shoji Nakamori Masato Sakon Keizo Dono Kenichi Wakasa Morito Monden |
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Affiliation: | Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. |
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Abstract: | BACKGROUND: Hepatocellular carcinoma (HCC) is a hypervascular tumor and angiogenesis plays an important role in its progression. Angiogenesis is regulated by a balance between pro and antiangiogenic molecules. The aim of this study was to investigate the expressions of angiogenic factors and elucidate their roles in angiogenesis in HCC. METHODS: We investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), hypoxia-induced factor-1alpha (HIF-1alpha) and thrombospondin-1 (TSP-1) in 60 specimens of surgically resected HCC. We investigated the relationship between their expressions and clinicopathological factors or prognosis. RESULTS: Ang-2 staining had a significant correlation with the grade of differentiation of HCC cells (P=0.0082). VEGF and Ang-2 expression correlated positively with microvessel density (MVD) (P=0.0061 and 0.0374, respectively). MVD of well-differentiated HCC were significantly lower than those of moderately and poorly differentiated HCC. The disease-free survival time of patients with high Ang-2 and/or HIF-1alpha expression was significantly shorter than that of the low expression group (P=0.0278 and 0.0374, respectively). CONCLUSION: Our study showed that the expression of VEGF and Ang-2 correlated with MVD. Strong Ang-2 expression and/or high nuclear expression of HIF-1alpha is a significant predictive factor for recurrence after curative resection in HCC patients. |
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Keywords: | angiogenesis angiopoietin hepatocellular carcinoma hypoxia‐induced factor vascular endothelial growth factor |
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