Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-2-5
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
(c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1451-8
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed-meshheading:17245699-Adenocarcinoma, pubmed-meshheading:17245699-Adult, pubmed-meshheading:17245699-Aged, pubmed-meshheading:17245699-Aged, 80 and over, pubmed-meshheading:17245699-Animals, pubmed-meshheading:17245699-Antigens, Neoplasm, pubmed-meshheading:17245699-Antineoplastic Agents, pubmed-meshheading:17245699-Breast Neoplasms, pubmed-meshheading:17245699-Carbonic Anhydrases, pubmed-meshheading:17245699-Carcinoma, Ductal, Breast, pubmed-meshheading:17245699-Carcinoma, Lobular, pubmed-meshheading:17245699-Carcinoma, Medullary, pubmed-meshheading:17245699-Chemotherapy, Adjuvant, pubmed-meshheading:17245699-Female, pubmed-meshheading:17245699-Humans, pubmed-meshheading:17245699-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:17245699-Immunoenzyme Techniques, pubmed-meshheading:17245699-Male, pubmed-meshheading:17245699-Mice, pubmed-meshheading:17245699-Mice, Nude, pubmed-meshheading:17245699-Middle Aged, pubmed-meshheading:17245699-Neoplasm Invasiveness, pubmed-meshheading:17245699-Prognosis, pubmed-meshheading:17245699-Survival Rate, pubmed-meshheading:17245699-Treatment Outcome, pubmed-meshheading:17245699-Tumor Markers, Biological
pubmed:year
2007
pubmed:articleTitle
HIF-1alpha and CA IX staining in invasive breast carcinomas: prognosis and treatment outcome.
pubmed:affiliation
Institute of Signalling, Developmental Biology and Cancer Research, University of Nice, Nice, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't