Overexpression of hypoxia-inducible factor HIF-1alpha predicts early relapse in breast cancer: retrospective study in a series of 745 patients.
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.
Dales
Jean-Philippe
JP
Department of Pathology, Hôpital Nord, Marseilles, France. Jdales@mail.ap-hm.fr
Garcia
Stéphane
S
Meunier-Carpentier
Séverine
S
Andrac-Meyer
Lucile
L
Haddad
Olivier
O
Lavaut
Marie-Noölle
MN
Allasia
Claude
C
Bonnier
Pascal
P
Charpin
Colette
C
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*
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