Bluff, J.E., Menakuru, S.R., Cross, S.S. orcid.org/0000-0003-2044-1754 et al. (5 more authors) (2009) Angiogenesis is associated with the onset of hyperplasia in human ductal breast disease. British Journal of Cancer, 101 (4). pp. 666-672. ISSN 0007-0920
Abstract
BACKGROUND: The precise timing of the angiogenic switch and the role of angiogenesis in the development of breast malignancy is currently unknown. METHODS: Therefore, the expression of CD31 (pan endothelial cells (ECs)), endoglin (actively proliferating ECs), hypoxia-inducible factor-1 (HIF-1alpha), vascular endothelial growth factor-A (VEGF) and tissue factor (TF) were quantified in 140 surgical specimens comprising normal human breast, benign and pre-malignant hyperplastic tissue, in situ and invasive breast cancer specimens. RESULTS: Significant increases in angiogenesis (microvessel density) were observed between normal and benign hyperplastic breast tissue (P<0.005), and between in situ and invasive carcinomas (P<0.0005). In addition, significant increases in proliferating ECs were observed in benign hyperplastic breast compared with normal breast (P<0.05) cancers and in invasive compared with in situ cancers (P<0.005). Hypoxia-inducible factor-1alpha, VEGF and TF expression were significantly associated with increases in both angiogenesis and proliferating ECs (P<0.05). Moreover, HIF-1alpha was expressed by 60-75% of the hyperplastic lesions, and a significant association was observed between VEGF and TF in ECs (P<0.005) and invasive tumour cells (P<0.01). CONCLUSIONS: These findings are the first to suggest that the angiogenic switch, associated with increases in HIF-1alpha, VEGF and TF expression, occurs at the onset of hyperplasia in the mammary duct, although the greatest increase in angiogenesis occurs with the development of invasion.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2009 Cancer Research UK From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
Keywords: | Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Cell Proliferation; Endothelial Cells; Female; Humans; Hyperplasia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Neovascularization, Pathologic; Precancerous Conditions; Prognosis; Thromboplastin; Tumor Markers, Biological; Vascular Endothelial Growth Factor A |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Apr 2016 11:08 |
Last Modified: | 11 Apr 2016 11:08 |
Published Version: | http://dx.doi.org/10.1038/sj.bjc.6605196 |
Status: | Published |
Publisher: | Cancer Research UK |
Refereed: | Yes |
Identification Number: | 10.1038/sj.bjc.6605196 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:80404 |
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