ArticlePloS one2013
HIF-1α overexpression in ductal carcinoma in situ of the breast in BRCA1 and BRCA2 mutation carriers.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.Cancer discovery · 2026Article
- Association analysis of germline mutations in CHEK2, PALB2, NBN and RECQL with the risk of ductal carcinoma in situ in Polish women.Hereditary cancer in clinical practice · 2025Article
- The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering.Cell communication and signaling : CCS · 2024Review
- Variable number tandem repeats (VNTRs) as modifiers of breast cancer risk in carriers of BRCA1 185delAG.European journal of human genetics : EJHG · 2023Article
- The role of hypoxia-inducible factor-1 alpha in multidrug-resistant breast cancer.Frontiers in oncology · 2022Review
- Plasma Metabolome Signature Indicative ofFrontiers in oncology · 2021Article
- HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer.The Journal of clinical investigation · 2020Review
- Article
- The prognostic significance of immune microenvironment in breast ductal carcinoma in situ.British journal of cancer · 2020Article
- Sensitization of Carboplatinum- and Taxol-Resistant High-Grade Serous Ovarian Cancer Cells Carrying p53, BRCA1/2 Mutations by Emblica officinalis (Amla) via Multiple Targets.Journal of Cancer · 2020Article
- Collagen (XI) alpha-1 chain is an independent prognostic factor in breast ductal carcinoma in situ.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- Geometric characteristics of collagen have independent prognostic significance in breast ductal carcinoma in situ: an image analysis study.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- Proteomics Analysis to Assess the Role of Mitochondria in BRCA1-Mediated Breast Tumorigenesis.Proteomes · 2018Article
- Expression of HIF-1α in medullary thyroid cancer identifies a subgroup with poor prognosis.Oncotarget · 2017Article
- Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer.Disease markers · 2016Article
- MiR-578 and miR-573 as potential players in BRCA-related breast cancer angiogenesis.Oncotarget · 2015Article
- New biomarkers to predict the evolution of in situ breast cancers.BioMed research international · 2014Article
- Hypoxia and human genome stability: downregulation of BRCA2 expression in breast cancer cell lines.BioMed research international · 2013Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have revealed that BRCA1 and BRCA2 germline mutation-related breast cancers show frequent overexpression of hypoxia inducible factor-1α (HIF-1α), the key regulator of the hypoxia response. However, the question remained whether hypoxia is a late stage bystander or a true carcinogenetic event in patients with hereditary predisposition. We therefore studied HIF-1α overexpression in ductal carcinoma in situ (DCIS), an established precursor of invasive breast cancer.We used immunohistochemistry to examine the expression of the hypoxia markers HIF-1α, CAIX and Glut-1 in DCIS and available invasive carcinoma lesions of 32 BRCA1, 16 BRCA2 and 77 non-BRCA mutation-related cases. HIF-1α expression was detected in 63% of BRCA1 and 62% of BRCA2 as compared to 34% of non-BRCA mutation-related DCIS cases (p = 0.005). CAIX overexpression was present in 56% of BRCA1 and 44% of BRCA2 as compared to 6% of non-BRCA mutation-related DCIS cases (p = 0.000). Glut-1 overexpression was observed in 59% of BRCA1, 75% of BRCA2 and 67% of non-BRCA mutation-related DCIS cases (p = 0.527). Overall, HIF-1α, CAIX and Glut-1 expression in BRCA mutation-related DCIS matched the expression in the accompanying invasive cancers in 60% or more of cases. In non-BRCA mutation-related cases the expression of the hypoxia markers in DCIS matched the expression in the invasive part in 46% or more of the cases.Although BRCA1 and BRCA2 germline mutation-related invasive breast cancers are different in many ways, the hypoxia-related proteins HIF-1α, CAIX and Glut-1 are expressed in both DCIS and invasive lesions of BRCA1 and BRCA2 mutation carriers. This suggests that hypoxia may already play a role in the DCIS stage of BRCA1 and BRCA2 germline mutation related breast carcinogenesis, and may also drive cancer progression. Hypoxia-related proteins are therefore putative targets for therapy and molecular imaging for early detection and monitoring therapy response in BRCA mutation patients.
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