Clinical Significance of Immunohistochemical Expression of Hypoxia-Inducible Factor–1α as a Prognostic Marker in Rectal Adenocarcinoma

BackgroundHypoxia-inducible factor–1α (HIF-1α), 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-1α and vascular endothelial growth factor (VEGF) and clinicopathologic characteristics, and evaluated the role of HIF-1α expression in patients with rectal adenocarcinoma.Patients and MethodsThe immunohistochemical expression of HIF-1α 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-1α with regard to the overall survival and local control endpoints was determined by univariate analyses.ResultsIncreased HIF-1α 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-1α 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-1α expression.ConclusionThese results show that HIF-1α might represent an important biologic marker evaluating the prognosis of patients with rectal adenocarcinoma.