Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer.
OBJECTIVE
Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that supports the adaptation of human cancer cells to hypoxia and is involved in various pathways supporting tumor growth and progression. The aim of this study was to determine the prognostic influence of HIF-1alpha expression in patients with advanced-stage breast cancer, evident by positive lymph nodes.


METHODS
Expression of HIF-1alpha was determined immunohistochemically in 206 patients with lymph node-positive breast cancer. Furthermore, the interrelationship of HIF-1alpha with p53 and HER-2 protein expression, estrogen receptor density, and survival was analyzed. Colocalization of p53 and HIF-1alpha proteins was analyzed by confocal laser scanning microscopy.


RESULTS
Strong nuclear expression of HIF-1alpha by invasive cancer cells was found in 48 patients (23.3%), moderate expression was found in 74 patients (35.9%), and weak expression was found in 35 patients (17%); no expression was observed in 49 patients (23.8%). HIF-1alpha protein overexpression was associated with significantly shorter overall and disease-free survival time (P = 0.003 and P = 0.001, respectively; Cox regression analysis). No correlation of HIF-1alpha and HER-2 expression or estrogen receptor density was observed.


CONCLUSIONS
This study shows that HIF-1alpha is an independent prognostic factor for an unfavorable prognosis in patients with lymph node-positive breast cancer. Our results indicate that patients with advanced-stage breast cancers might profit from future therapies targeting HIF-1alpha.
Schindl
Monika
M
Institute of Clinical Pathology, Department of Surgery, University of Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Schoppmann
Sebastian F
SF
Samonigg
Hellmut
H
Hausmaninger
Hubert
H
Kwasny
Werner
W
Gnant
Michael
M
Jakesz
Raimund
R
Kubista
Ernst
E
Birner
Peter
P
Oberhuber
Georg
G
D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D018613:Microscopy, Confocal; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C497442:HIF1A protein, human