Overexpression of Hypoxia-Inducible Factor-1α in Human Osteosarcoma: Correlation with Clinicopathological Parameters and Survival Outcome

Abstract

Hypoxia is a common feature of many solid cancers and linked to malignant transformation, metastases and treatment resistance. Hypoxia is known to induce hypoxia-inducible factor-1alpha (HIF-1alpha) expression. The aim of this study is to investigate the impact of overexpression of HIF-1alpha on prognosis and the relationship with clinicopathological characteristics in human osteosarcoma. Immunochemistry with digital image analysis was used to determine the HIF-1alpha protein expression in histologic sections from 39 treated patients. According to our study, expression of HIF-1alpha protein were detected in 31 of 39 cases (79%), with signal concentrated primarily within the nuclei of tumor cell. In contrast, non-cancerous adjacent tissues showed no HIF-1alpha immunoreactivity. HIF-1alpha expression was significantly associated with surgical stage, percentage of dead cells and microvessel density (MVD). Surgical stage, percentage of dead cells and HIF-1alpha expression showed significant influence on overall survival (OS) and disease-free survival (DFS) in univariate analysis. In multivariate analysis, surgical stage (IIA versus IIB/III) and percentage of dead cells (<90% versus > or =90%) were significant for DFS and OS. Those patients with HIF-1alpha moderate/strong expression showed significantly shorter OS and DFS compared with HIF-1alpha negative/weak expression. Overexpression of HIF-1alpha is predictive of a poor outcome and might be a novel therapeutic target in human osteosarcoma.