Levels of hypoxia‐inducible factor‐1α independently predict prognosis in patients with lymph node negative breast carcinoma
Open accessAbstract
BACKGROUND: Hypoxia‐inducible factor‐1 (HIF‐1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis to survive cellular hypoxia. Increased levels of HIF‐1α, the O 2 ‐regulated subunit of HIF‐1, were noted during breast carcinogenesis. In this study, the prognostic value of HIF‐1α expression and its correlation with various clinicopathologic variables in patients with invasive breast carcinoma were investigated. METHODS: Expression levels of HIF‐1α, HER‐2/ neu , estrogen receptor, and progesterone receptor were analyzed in 150 patients with early‐stage breast carcinoma by immunohistochemistry. HER‐2/ neu gene amplification was investigated with automated fluorescent in situ hybridization. The mitotic activity index, histologic grade, and tumor type were assessed in hematoxylin and eosinstained specimens. Clinical data included disease‐free survival, overall survival, lymph node status, and tumor size. The data were analyzed with two‐sided univariate and multivariate tests, with P values < 0.05 considered significant. RESULTS: High levels of HIF‐1α had an association of borderline significance with decreased overall survival ( P = 0.059) and disease‐free survival ( P = 0.110) that was ascribed completely to the subgroup of women with lymph node negative tumors ( n = 81 patients; P = 0.008 and P = 0.004, respectively). HER‐2/ neu immunoreactivity ( P < 0.001) and gene amplification ( P < 0.001), vascular endothelial growth factor expression ( P = 0.016), and Ki‐67 expression ( P < 0.001) were correlated strongly with HIF‐1α positivity, although none of those factors had an independent effect on survival. CONCLUSIONS: Increased levels of HIF‐1α were associated independently with shortened survival in patients with lymph node negative breast carcinoma. Therefore, the use of immunohistochemical assessment of HIF‐1α as a new predictor of poor outcome may improve clinical decision‐making regarding adjuvant treatment of patients with lymph node negative breast carcinoma. Cancer 2003;97:1573–81. © 2003 American Cancer Society. DOI 10.1002/cncr.11246
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Increased HIF-1α protein levels in tumor biopsies are linked with increased risk of metastasis and mortality in lymph node-positive, lymph node-negative, HER2-positive, estrogen receptor-positive, and unselected breast cancer patients.
“Immunohistochemical studies of tumor biopsies have linked increased HIF-1α protein levels with increased risk of metastasis [14] and mortality in lymph node-positive [15], lymph node-negative [16], HER2-positive [17], estrogen receptor-positive [18], and unselected [14, 19] breast cancer patients.”
From The hypoxic tumor microenvironment: A driving force for breast cancer progression (2016) · cites this paper as [16]
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- Authors
- Bos, R., van der Groep, P., Greijer, A. E., Shvarts, A., Meijer, S., Pinedo, H. M., Semenza, G. L., van Diest, P. J., & van der Wall, E.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Johns Hopkins University (US)
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2003-03-03
- Volume
- 97
- Issue
- 6
- Pages
- 1573-1581
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- OpenAlex
- W2120807407
- Cited by
- 500
- References
- 42
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 10 · 2023: 13 · 2022: 15 · 2021: 21 · 2020: 18 · 2019: 25 · 2018: 17 · 2017: 19 · 2016: 24 · 2015: 18 · 2014: 22 · 2013: 39 · 2012: 22
- FWCI
- 10.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- 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
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Keywords
- hypoxia-inducible factor-1α, prognostic factors, overall survival, disease-free survival, HER2/neu, estrogen receptor, progesterone receptor, vascular endothelial growth factor, Ki-67, tumor hypoxia, adjuvant treatment decision-making
- MeSH terms
- Adult, Aged, Aged, 80 and over, Breast Neoplasms, Carcinoma, DNA-Binding Proteins, Female, Follow-Up Studies, Humans, Immunohistochemistry, Lymphatic Metastasis, Middle Aged, Mitotic Index, Nuclear Proteins, Predictive Value of Tests, Prognosis, Receptors, Estrogen, Receptors, Progesterone, Transcription Factors, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, In Situ Hybridization, Fluorescence, Helix-Loop-Helix Motifs, Disease-Free Survival, Erb-b2 Receptor Tyrosine Kinases, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
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