Expression of hypoxia-inducible factor-1 alpha (HIF-1α) in patients with the gallbladder carcinoma

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. 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-1 alpha and VEGF were evaluated by immunohistochemistry, and correlations between the expression of these factors and clinicopathological features including prognosis were analyzed. Among 31 specimens from patients with gallbladder carcinoma, 22 (70%) and 9 (30%) were positive for HIF-1 alpha and VEGF expression, respectively. Expression of HIF-1 alpha 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-1 alpha positive staining was significantly lower than that for patients with HIF-1 alpha negative staining. However, VEGF overexpression did not correlate with clinical outcomes. We demonstrated that HIF-1 alpha expression was associated with a malignant behavior risk category in gallbladder cancer. Expression of HIF-1 alpha was correlated with the poor prognostic indicators, such as lymph node metastasis and venous invasion. Therefore, HIF-1 alpha could serve as an auxiliary parameter for predicting malignant behavior for gallbladder carcinomas.