BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a central role in biologic processes under hypoxic conditions, especially concerning tumor angiogenesis. Vascular endothelial growth factor (VEGF) is a potent proangiogenic agent and a multifunctional angiogenic cytokine in many malignant tumors. METHODS: This study was conducted to clarify the role of HIF-1 expression in gallbladder carcinoma. Thirty-one patients with gallbladder carcinoma underwent surgical treatment between 1994 and 2003 at the Department of Surgery, University of Tokushima, Japan. Both HIF-1alpha and VEGF were evaluated by immunohistochemistry, and correlations between the expression of these factors and clinicopathological features including prognosis were analyzed. RESULTS: Among 31 specimens from patients with gallbladder carcinoma, 22 (70%) and 9 (30%) were positive for HIF-1alpha and VEGF expression, respectively. Expression of HIF-1alpha was significantly correlated with stage, tumor curability, lymph node metastasis, venous invasion, hepatic infiltration, and lymphatic invasion (P < 0.05). The survival rate for patients with HIF-1alpha positive staining was significantly lower than that for patients with HIF-1alpha negative staining. However, VEGF overexpression did not correlate with clinical outcomes. We demonstrated that HIF-1alpha expression was associated with a malignant behavior risk category in gallbladder cancer. CONCLUSION: Expression of HIF-1alpha was correlated with the poor prognostic indicators, such as lymph node metastasis and venous invasion. Therefore, HIF-1alpha could serve as an auxiliary parameter for predicting malignant behavior for gallbladder carcinomas.
BACKGROUND:Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a central role in biologic processes under hypoxic conditions, especially concerning tumor angiogenesis. Vascular endothelial growth factor (VEGF) is a potent proangiogenic agent and a multifunctional angiogenic cytokine in many malignant tumors. METHODS: This study was conducted to clarify the role of HIF-1 expression in gallbladder carcinoma. Thirty-one patients with gallbladder carcinoma underwent surgical treatment between 1994 and 2003 at the Department of Surgery, University of Tokushima, Japan. Both HIF-1alpha and VEGF were evaluated by immunohistochemistry, and correlations between the expression of these factors and clinicopathological features including prognosis were analyzed. RESULTS: Among 31 specimens from patients with gallbladder carcinoma, 22 (70%) and 9 (30%) were positive for HIF-1alpha and VEGF expression, respectively. Expression of HIF-1alpha was significantly correlated with stage, tumor curability, lymph node metastasis, venous invasion, hepatic infiltration, and lymphatic invasion (P < 0.05). The survival rate for patients with HIF-1alpha positive staining was significantly lower than that for patients with HIF-1alpha negative staining. However, VEGF overexpression did not correlate with clinical outcomes. We demonstrated that HIF-1alpha expression was associated with a malignant behavior risk category in gallbladder cancer. CONCLUSION: Expression of HIF-1alpha was correlated with the poor prognostic indicators, such as lymph node metastasis and venous invasion. Therefore, HIF-1alpha could serve as an auxiliary parameter for predicting malignant behavior for gallbladder carcinomas.
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