RGD Reference Report - HIF-1alpha and CA IX staining in invasive breast carcinomas: prognosis and treatment outcome. - Rat Genome Database

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HIF-1alpha and CA IX staining in invasive breast carcinomas: prognosis and treatment outcome.

Authors: Trastour, C  Benizri, E  Ettore, F  Ramaioli, A  Chamorey, E  Pouyssegur, J  Berra, E 
Citation: Trastour C, etal., Int J Cancer. 2007 Apr 1;120(7):1451-8.
RGD ID: 2293195
Pubmed: PMID:17245699   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.22436   (Journal Full-text)

Hypoxia stabilizes HIF-1alpha (Hypoxia Inducible Factor-1alpha), which then triggers the expression of several genes involved in many aspects of cancer progression, including metabolic adaptation, cell survival and angiogenesis. The aim of our study was to evaluate the impact of HIF-1alpha and CA IX (carbonic anhydrase IX) (one of its target genes) expression on prognosis and treatment outcome of patients with breast cancer. Because of the extreme O2-dependent instability of the protein, we first validated HIF-1alpha staining using xenograft tumours that were subjected to experimental conditions mimicking surgical clamping or sitting at room temperature under normoxic conditions after surgical excision but before fixation. Afterwards, the immunohistochemical staining of HIF-1alpha and CA IX was evaluated in 132 invasive breast carcinomas with a 10-year follow-up, and correlated to classical clinicopathological parameters and response to adjuvant therapy. No significant correlation was found between tumour size or nodal status and the expression of HIF-1alpha or CA IX. Statistically significant association was found between HIF-1alpha or CA IX staining and the grade, hormonal receptors loss and the presence of carcinoma in situ. Overexpression of HIF-1alpha and CA IX correlates with a poor prognosis in breast cancer. We show that HIF-1alpha is an independent prognostic factor for distant metastasis-free survival and disease-free survival in multivariate analysis. Furthermore, overexpression of HIF-1alpha or CA IX correlates with a poor outcome after conventional adjuvant therapy. CA IX is, however, a weaker prognostic and predictive factor than HIF-1alpha, and its association with HIF-1alpha does not modify the survival curve neither response to therapy, compared to HIF-1alpha alone.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CA9Humanbreast carcinoma disease_progressionIEP  RGD 
Car9Ratbreast carcinoma disease_progressionISOCA9 (Homo sapiens) RGD 
Car9Mousebreast carcinoma disease_progressionISOCA9 (Homo sapiens) RGD 
HIF1AHumanBreast Neoplasms disease_progressionIEP  RGD 
Hif1aRatBreast Neoplasms disease_progressionISOHIF1A (Homo sapiens) RGD 
Hif1aMouseBreast Neoplasms disease_progressionISOHIF1A (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Car9  (carbonic anhydrase 9)
Hif1a  (hypoxia inducible factor 1 subunit alpha)

Genes (Mus musculus)
Car9  (carbonic anhydrase 9)
Hif1a  (hypoxia inducible factor 1, alpha subunit)

Genes (Homo sapiens)
CA9  (carbonic anhydrase 9)
HIF1A  (hypoxia inducible factor 1 subunit alpha)


Additional Information