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Japanese Journal of Clinical Oncology Advance Access originally published online on January 19, 2007
Japanese Journal of Clinical Oncology 2007 37(2):127-134; doi:10.1093/jjco/hyl137
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© 2007 Foundation for Promotion of Cancer Research

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

Qing-Cheng Yang1, Bing-Fang Zeng1,, Yang Dong1, Zhong-Min Shi1, Zhi-Ming Jiang2 and Jin Huang2

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{alpha} (HIF-1{alpha}) expression. The aim of this study is to investigate the impact of overexpression of HIF-1{alpha} on prognosis and the relationship with clinicopathological characteristics in human osteosarcoma.

Methods: Immunochemistry with digital image analysis was used to determine the HIF-1{alpha} protein expression in histologic sections from 39 treated patients.

Results: According to our study, expression of HIF-1{alpha} 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{alpha} immunoreactivity. HIF-1{alpha} expression was significantly associated with surgical stage, percentage of dead cells and microvessel density (MVD). Surgical stage, percentage of dead cells and HIF-1{alpha} 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{alpha} moderate/strong expression showed significantly shorter OS and DFS compared with HIF-1{alpha} negative/weak expression.

Conclusions: Overexpression of HIF-1{alpha} is predictive of a poor outcome and might be a novel therapeutic target in human osteosarcoma.

Key Words: osteosarcoma • HIF-1{alpha} • prognosis • immunochemistry


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