title: Overexpression of hypoxia-inducible factor HIF-1alpha predicts early relapse in breast cancer: retrospective study in a series of 745 patients.
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.
authors.affiliation: Department of Pathology, Hôpital Nord, Marseilles, France. Jdales@mail.ap-hm.fr
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Dales
authors.forename: Stéphane
authors.initials: S
authors.lastname: Garcia
authors.forename: Séverine
authors.initials: S
authors.lastname: Meunier-Carpentier
authors.forename: Lucile
authors.initials: L
authors.lastname: Andrac-Meyer
authors.forename: Olivier
authors.initials: O
authors.lastname: Haddad
authors.forename: Marie-Noölle
authors.initials: MN
authors.lastname: Lavaut
authors.forename: Claude
authors.initials: C
authors.lastname: Allasia
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonnier
authors.forename: Colette
authors.initials: C
authors.lastname: Charpin
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D012189:Retrospective Studies; D014157:Transcription Factors / Q000032:analysis*
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors