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Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers
Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression o...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858119/ https://www.ncbi.nlm.nih.gov/pubmed/27499891 http://dx.doi.org/10.1002/cjp2.6 |
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author | Aradottir, Margret Reynisdottir, Sigridur T Stefansson, Olafur A Jonasson, Jon G Sverrisdottir, Asgerdur Tryggvadottir, Laufey Eyfjord, Jorunn E Bodvarsdottir, Sigridur K |
author_facet | Aradottir, Margret Reynisdottir, Sigridur T Stefansson, Olafur A Jonasson, Jon G Sverrisdottir, Asgerdur Tryggvadottir, Laufey Eyfjord, Jorunn E Bodvarsdottir, Sigridur K |
author_sort | Aradottir, Margret |
collection | PubMed |
description | Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild‐type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer‐specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23–40.6; p = 0.028). Poor breast cancer‐specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19–85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81–51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A targeted treatment. |
format | Online Article Text |
id | pubmed-4858119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48581192016-08-05 Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers Aradottir, Margret Reynisdottir, Sigridur T Stefansson, Olafur A Jonasson, Jon G Sverrisdottir, Asgerdur Tryggvadottir, Laufey Eyfjord, Jorunn E Bodvarsdottir, Sigridur K J Pathol Clin Res Original Articles Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild‐type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer‐specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23–40.6; p = 0.028). Poor breast cancer‐specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19–85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81–51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A targeted treatment. John Wiley and Sons Inc. 2014-11-07 /pmc/articles/PMC4858119/ /pubmed/27499891 http://dx.doi.org/10.1002/cjp2.6 Text en © 2014 John Wiley and Sons Ltd and The Pathological Society of Great Britain and Ireland This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/3.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Aradottir, Margret Reynisdottir, Sigridur T Stefansson, Olafur A Jonasson, Jon G Sverrisdottir, Asgerdur Tryggvadottir, Laufey Eyfjord, Jorunn E Bodvarsdottir, Sigridur K Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers |
title | Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers |
title_full | Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers |
title_fullStr | Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers |
title_full_unstemmed | Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers |
title_short | Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers |
title_sort | aurora a is a prognostic marker for breast cancer arising in brca2 mutation carriers |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858119/ https://www.ncbi.nlm.nih.gov/pubmed/27499891 http://dx.doi.org/10.1002/cjp2.6 |
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