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Overexpression of hypoxia-inducible factor HIF-1alpha predicts early relapse in breast cancer: retrospective study in a series of 745 patients.
- Source :
-
International journal of cancer [Int J Cancer] 2005 Sep 20; Vol. 116 (5), pp. 734-9. - Publication Year :
- 2005
-
Abstract
- Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that is involved in tumour growth and metastasis by regulating genes involved in response to hypoxia. HIF-1alpha protein overexpression has been shown in a variety of human cancers, but only 2 studies have documented the prognostic relevance of HIF-1alpha expression in breast cancer. The aim of our study was to determine accurately the impact of HIF-1alpha expression on prognosis in a large series (n = 745) of unselected patients with invasive breast cancer in terms of overall survival, local recurrence and distant metastasis risk. HIF-1alpha expression was investigated using immunohistochemical assays on frozen sections, and correlated with patients' outcome (median follow-up = 13.5 years). Univariate (Kaplan-Meier) analysis showed that high levels of HIF-1alpha expression (cutoff = 10%) significantly correlated with poor overall survival (p = 0.019). HIF-1alpha expression correlated with high metastasis risk among the whole group of patients (p = 0.008). Multivariate analysis (Cox model) showed that the HIF-1alpha predictive value was independent of other current prognostic indicators. Moreover among node negative ones, HIF-1alpha expression was also significantly predictive of metastasis risk (p = 0.03) and of relapse (p = 0.035). All the data suggest that HIF-1alpha is associated with a worse prognosis in patients with invasive breast carcinoma. Furthermore HIF-1alpha immunodetection may be considered as a potential indicator for selecting patients who could benefit from specific therapies interfering with HIF-1alpha pathway.<br /> ((c) 2005 Wiley-Liss, Inc.)
- Subjects :
- Adult
Aged
Breast Neoplasms pathology
Female
Humans
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Immunohistochemistry
Middle Aged
Neoplasm Metastasis
Neoplasm Recurrence, Local
Prognosis
Retrospective Studies
Breast Neoplasms chemistry
DNA-Binding Proteins analysis
Nuclear Proteins analysis
Transcription Factors analysis
Subjects
Details
- Language :
- English
- ISSN :
- 0020-7136
- Volume :
- 116
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 15849727
- Full Text :
- https://doi.org/10.1002/ijc.20984