VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.

Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is know...

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Autores principales: Concetta Saponaro, Andrea Malfettone, Girolamo Ranieri, Katia Danza, Giovanni Simone, Angelo Paradiso, Anita Mangia
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:ab26d5908b67434d95e177b60285c75f2021-11-18T08:01:52ZVEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.1932-620310.1371/journal.pone.0053070https://doaj.org/article/ab26d5908b67434d95e177b60285c75f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23326384/?tool=EBIhttps://doaj.org/toc/1932-6203Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is known that there is an interaction between HIF-1α and BRCA1 carrier cancers, but little has been reported about angiogenesis in BRCA1-2 carrier and BRCAX breast cancers. In this study, we investigated the expression of VEGF and HIF-1α and microvessel density (MVD) in 26 BRCA1-2 carriers and 58 BRCAX compared to 77 sporadic breast cancers, by immunohistochemistry. VEGF expression in BRCA1-2 carriers was higher than in BRCAX cancer tissues (p = 0.0001). Furthermore, VEGF expression was higher in both BRCA1-2 carriers and BRCAX than the sporadic group (p<0.0001). VEGF immunoreactivity was correlated with poor tumor grade (p = 0.0074), hormone receptors negativity (p = 0.0206, p = 0.0002 respectively), and MIB-1-labeling index (p = 0.0044) in familial cancers (BRCA1-2 and BRCAX). The percentage of nuclear HIF-1α expression was higher in the BRCA1-2 carriers than in BRCAX cancers (p<0.05), and in all familial than in sporadic tumor tissues (p = 0.0045). A higher MVD was observed in BRCA1-2 carrier than in BRCAX and sporadic cancer tissues (p = 0.002, p = 0.0001 respectively), and in all familial tumors than in sporadic tumors (p = 0.01). MVD was positively related to HIF-1α expression in BRCA1-2 carriers (r = 0.521, p = 0.006), and, in particular, we observed a highly significant correlation in the familial group (r = 0.421, p<0.0001). Our findings suggest that angiogenesis plays a crucial role in BRCA1-2 carrier breast cancers. Prospective studies in larger BRCA1-2 carrier series are needed to improve the best therapeutic strategies for this subgroup of breast cancer patients.Concetta SaponaroAndrea MalfettoneGirolamo RanieriKatia DanzaGiovanni SimoneAngelo ParadisoAnita MangiaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53070 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Concetta Saponaro
Andrea Malfettone
Girolamo Ranieri
Katia Danza
Giovanni Simone
Angelo Paradiso
Anita Mangia
VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.
description Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is known that there is an interaction between HIF-1α and BRCA1 carrier cancers, but little has been reported about angiogenesis in BRCA1-2 carrier and BRCAX breast cancers. In this study, we investigated the expression of VEGF and HIF-1α and microvessel density (MVD) in 26 BRCA1-2 carriers and 58 BRCAX compared to 77 sporadic breast cancers, by immunohistochemistry. VEGF expression in BRCA1-2 carriers was higher than in BRCAX cancer tissues (p = 0.0001). Furthermore, VEGF expression was higher in both BRCA1-2 carriers and BRCAX than the sporadic group (p<0.0001). VEGF immunoreactivity was correlated with poor tumor grade (p = 0.0074), hormone receptors negativity (p = 0.0206, p = 0.0002 respectively), and MIB-1-labeling index (p = 0.0044) in familial cancers (BRCA1-2 and BRCAX). The percentage of nuclear HIF-1α expression was higher in the BRCA1-2 carriers than in BRCAX cancers (p<0.05), and in all familial than in sporadic tumor tissues (p = 0.0045). A higher MVD was observed in BRCA1-2 carrier than in BRCAX and sporadic cancer tissues (p = 0.002, p = 0.0001 respectively), and in all familial tumors than in sporadic tumors (p = 0.01). MVD was positively related to HIF-1α expression in BRCA1-2 carriers (r = 0.521, p = 0.006), and, in particular, we observed a highly significant correlation in the familial group (r = 0.421, p<0.0001). Our findings suggest that angiogenesis plays a crucial role in BRCA1-2 carrier breast cancers. Prospective studies in larger BRCA1-2 carrier series are needed to improve the best therapeutic strategies for this subgroup of breast cancer patients.
format article
author Concetta Saponaro
Andrea Malfettone
Girolamo Ranieri
Katia Danza
Giovanni Simone
Angelo Paradiso
Anita Mangia
author_facet Concetta Saponaro
Andrea Malfettone
Girolamo Ranieri
Katia Danza
Giovanni Simone
Angelo Paradiso
Anita Mangia
author_sort Concetta Saponaro
title VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.
title_short VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.
title_full VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.
title_fullStr VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.
title_full_unstemmed VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.
title_sort vegf, hif-1α expression and mvd as an angiogenic network in familial breast cancer.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/ab26d5908b67434d95e177b60285c75f
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