Japanese Journal of Clinical Oncology Advance Access published online on January 19, 2007
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyl137
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© 2007 Foundation for Promotion of Cancer Research
Overexpression of Hypoxia-Inducible Factor-1
in Human Osteosarcoma: Correlation with Clinicopathological Parameters and Survival Outcome
1 Department of Orthopedics
2 Department of Pathology, Shanghai Sixth People's Hospital of Shanghai JiaoTong University, Shanghai, China
For reprints and all correspondence: Bing-Fang Zeng, Department of Orthopedics, Shanghai Sixth People's Hospital of Shanghai JiaoTong University, Yishan Road No. 600, Shanghai, 200233, China. E-mail: bingfangzeng{at}yahoo.com.cn
Received May 4, 2006; accepted September 29, 2006
BACKGROUND: 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-1
(HIF-1
) expression. The aim of this study is to investigate the impact of overexpression of HIF-1
on prognosis and the relationship with clinicopathological characteristics in human osteosarcoma.
METHODS: Immunochemistry with digital image analysis was used to determine the HIF-1
protein expression in histologic sections from 39 treated patients.
RESULTS: According to our study, expression of HIF-1
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-1
immunoreactivity. HIF-1
expression was significantly associated with surgical stage, percentage of dead cells and microvessel density (MVD). Surgical stage, percentage of dead cells and HIF-1
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
90%) were significant for DFS and OS. Those patients with HIF-1
moderate/strong expression showed significantly shorter OS and DFS compared with HIF-1
negative/weak expression.
CONCLUSIONS: Overexpression of HIF-1
is predictive of a poor outcome and might be a novel therapeutic target in human osteosarcoma.
Key Words: osteosarcoma HIF-1
prognosis immunochemistry