Clinical significance of immunohistochemical expression of hypoxia-inducible factor-l alpha as a prognostic marker in rectal adenocarcinoma

Background: Hypoxia-inducible factor-1 alpha (HIF-1 alpha), a subunit of hypoxia-inducible factor-1 (HIF-1), furnishes tumor cells with the means of adapting to stress parameters, such as tumor hypoxia, and promotes critical steps in tumor progression and aggressiveness by inducing angiogenesis and regulating energy metabolism. In this study, we investigated the relationship between HIF-1 alpha and vascular endothelial growth factor (VEGF) and clinicopathologic characteristics, and evaluated the role of HIF-1 alpha expression in patients with rectal adenocarcinoma. Patients and Methods: The immunohistochemical expression of HIF-1 alpha and VEGF was evaluated in 30 formalin-fixed, paraffin-embedded postoperative rectal adenocarcinoma tissue samples. Correlations with clinicopathologic characteristics were determined by cross-tabulations. The impact of the immunoreactivity of HIF-1 alpha with regard to the overall survival and local control endpoints was determined by univariate analyses. Results: Increased HIF-1 alpha expression was strongly associated with VEGF positivity (P = 0.002), Dukes stage (P = 0.017),and lymph node metastasis (P = 0.001). No correlation was found between the level of HIF-1 alpha expression and histologic grade (P = 0.63). The Kaplan-Meier curves showed a significantly shorter overall survival (P = 0.0087) and local control (P = 0.0438) for patients with high HIF-1 alpha expression. Conclusion: These results show that HIF-1 alpha might represent an important biologic marker evaluating the prognosis of patients with rectal adenocarcinoma.