Overexpression of hypoxia-inducible factor-1α in human osteosarcoma: Correlation with clinicopathological parameters and survival outcome

Abstract

Background: Hypoxia is a common feature of many solid cancers and linked to malignant transformation, metastases and treatment resistance. Hypoxia is known to induce hypoxiainducible factor-1 a (HIF-1α) expression. The aim of this study is to investigate the impact overexpression of HIF-1α on prognosis and the relationship with clinicopathological characteristics in human osteosarcoma. Methods: Immunochemistry with digital image analysis was used to determine the HIF-protein expression in histologic sections from 39 treated patients. Results: According to our study, expression of HIF-1α protein were detected in 31 cases (79%), with signal concentrated primarily within the nuclei of tumor cell. In contrast, non-cancerous adjacent tissues showed no HIF-1α immunoreactivity. HIF-1 α expression significantly associated with surgical stage, percentage of dead cells and microvessel density (MVD). Surgical stage, percentage of dead cells and HIF-1α expression showed significant influence on overall survival (OS) and disease-free survival (DFS) in univariate analysis. multivariate analysis, surgical stage (IIA versus IIB/III) and percentage of dead cells (<90% versus ≥90%) were significant for DFS and OS. Those patients with HIF-1 α moderate/strong expression showed significantly shorter OS and DFS compared with HIF-1α negative/expression. Conclusions: Overexpression of HIF-1α is predictive of a poor outcome and might novel therapeutic target in human osteosarcoma. © 2007 Foundation for Promotion of Cancer Research.