Hypoxia-inducible factor 1α is closely linked to an aggressive phenotype in breast cancer

Yamamoto, Yutaka; Ibusuki, Mutsuko; Okumura, Yasuhiro; Kawasoe, Teru; Kai, Kazuharu; Iyama, Kenichi; Iwase, Hirotaka

doi:10.1007/s10549-007-9742-1

Cited by 151Cancer, Hypoxia, and MetabolismBreast Cancer Treatment StudiesAngiogenesis and VEGF in Cancer

Hypoxia-inducible factor 1α is closely linked to an aggressive phenotype in breast cancer

Yamamoto, Yutaka, Ibusuki, Mutsuko, Okumura, Yasuhiro, Kawasoe, Teru, Kai, Kazuharu, Iyama, Kenichi, Iwase, Hirotaka·2008·Breast Cancer Research and Treatment

DOI 10.1007/s10549-007-9742-1

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Abstract

Purpose The aim of this study is to clarify characteristics of invasive breast cancer with expression of Hypoxia-induced factor 1alpha (HIF-1alpha) which is induced by hypoxia and signal transduction of growth factors.Experimental design We examined, by immunohistochemical analysis, the expression of HIF-1alpha in normal breast tissue, benign disorders and breast cancer. In invasive breast cancer, we investigated the correlation between expression of HIF-1alpha and clinicopathological and biological factors. We also studied the prognostic value of HIF-1alpha in breast cancer.Results HIF-1alpha was mainly detected in tumor cell nuclei. In the 171 cases of invasive breast cancer examined, nuclear HIF-1alpha expression was detected in 63 (36.8%) cases. Immunoreactive nuclear HIF-1alpha was correlated with tumor size (p = 0.0013), lymph node metastasis (p = 0.0005), tumor stage (p = 0.0031) and histological grade (p = 0.0074). Elevated HIF-1alpha levels was also associated with hormone receptor negativity (p = 0.0025), HER2 overexpression (p = 0.0053), high Ki67 labeling index (p = 0.0002), increased levels of VEGF (p < 0.0001), COX-2 overexpression (p = 0.0029) and increased nuclear p53 (p = 0.0048). In terms of the possible use of HIF-1alpha as a prognostic indicator, patients who had increased HIF-1alpha levels in their tumor showed shorter disease-free survival (DFS) (p < 0.0001) and overall survival (OS) (p = 0.0002) than those lacking HIF-1alpha in univariate analysis. In multivariate analysis of DFS and OS, HIF-1alpha was identified an independent prognostic factor.Conclusions These findings suggest that HIF-1alpha was closely linked to an aggressive phenotype in breast cancer. It may be useful to study the expression of HIF-1alpha using immunohistochemical analysis for better understanding of the tumor characteristics of breast cancer.

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Clinically, hypoxia is associated with HIF activation, metastasis, resistance to chemotherapy and radiotherapy, and poor patient survival.
“Clinically, hypoxia is associated with HIF activation, metastasis, and resistance to chemotherapy and radiotherapy, as well as poor patient survival”
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Authors: Yamamoto, Y., Ibusuki, M., Okumura, Y., Kawasoe, T., Kai, K., Iyama, K., & Iwase, H.
Affiliations: Kumamoto University (JP)
Corresponding author: Yamamoto, Yutaka
ORCID: Yamamoto, Yutaka
Okumura, Yasuhiro
Venue: Breast Cancer Research and Treatment
Publisher: Springer Science and Business Media LLC
Published: 2007-09-06
Volume: 110
Issue: 3
Pages: 465-475
ISSN: 0167-6806 (ISSN-L)
1573-7217
DOI: 10.1007/s10549-007-9742-1
OpenAlex: W2057742754
Cited by: 151
References: 50
Citations by year: 2026: 2 · 2025: 8 · 2024: 2 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 6 · 2015: 11 · 2014: 8 · 2013: 21 · 2012: 5
FWCI: 2.00
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Breast Cancer Research and Treatment (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords: hypoxia-inducible factor-1α, invasive breast cancer, tumor aggressiveness, prognostic factors, tumor hypoxia, lymph node metastasis, hormone receptor-negative breast cancer, HER2 overexpression, Ki-67 proliferation index, vascular endothelial growth factor, cyclooxygenase-2, p53, disease-free survival, overall survival
MeSH terms: Breast Diseases, Breast Neoplasms, Female, Humans, Immunohistochemistry, Middle Aged, Phenotype, Biomarkers, Tumor, Carcinoma, Ductal, Breast, Hypoxia-Inducible Factor 1, alpha Subunit, Kaplan-Meier Estimate

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Hypoxia-inducible factor 1α is closely linked to an aggressive phenotype in breast cancer

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