Overexpression of hypoxia-inducible factor-1alpha in human osteosarcoma: correlation with clinicopathological parameters and survival outcome.
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-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.


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


RESULTS
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.


CONCLUSIONS
Overexpression of HIF-1alpha is predictive of a poor outcome and might be a novel therapeutic target in human osteosarcoma.
Yang
Qing-Cheng
QC
Department of Orthopedics, Shanghai Sixth People's Hospital of Shanghai JiaoTong University, Shanghai, China.
Zeng
Bing-Fang
BF
Dong
Yang
Y
Shi
Zhong-Min
ZM
Jiang
Zhi-Ming
ZM
Huang
Jin
J
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis
D051795:Hypoxia-Inducible Factor 1, alpha Subunit