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FOXA1 and AR in invasive breast cancer: new findings on their co-expression and impact on prognosis in ER-positive patients

BACKGROUND: The role of forkhead-box A1 (FOXA1) and Androgen receptor (AR) in breast cancer (BC) has been extensively studied. However, the prognostic role of their co-expression in Estrogen receptor positive (ER+) BC has not been investigated so far. The aim of the present study was thus to assess...

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Autores principales: Rangel, Nelson, Fortunati, Nicoletta, Osella-Abate, Simona, Annaratone, Laura, Isella, Claudio, Catalano, Maria Graziella, Rinella, Letizia, Metovic, Jasna, Boldorini, Renzo, Balmativola, Davide, Ferrando, Pietro, Marano, Francesca, Cassoni, Paola, Sapino, Anna, Castellano, Isabella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029370/
https://www.ncbi.nlm.nih.gov/pubmed/29970021
http://dx.doi.org/10.1186/s12885-018-4624-y
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author Rangel, Nelson
Fortunati, Nicoletta
Osella-Abate, Simona
Annaratone, Laura
Isella, Claudio
Catalano, Maria Graziella
Rinella, Letizia
Metovic, Jasna
Boldorini, Renzo
Balmativola, Davide
Ferrando, Pietro
Marano, Francesca
Cassoni, Paola
Sapino, Anna
Castellano, Isabella
author_facet Rangel, Nelson
Fortunati, Nicoletta
Osella-Abate, Simona
Annaratone, Laura
Isella, Claudio
Catalano, Maria Graziella
Rinella, Letizia
Metovic, Jasna
Boldorini, Renzo
Balmativola, Davide
Ferrando, Pietro
Marano, Francesca
Cassoni, Paola
Sapino, Anna
Castellano, Isabella
author_sort Rangel, Nelson
collection PubMed
description BACKGROUND: The role of forkhead-box A1 (FOXA1) and Androgen receptor (AR) in breast cancer (BC) has been extensively studied. However, the prognostic role of their co-expression in Estrogen receptor positive (ER+) BC has not been investigated so far. The aim of the present study was thus to assess the co-expression (protein and mRNA) of FOXA1 and AR in BC patients, in order to evaluate their prognostic impact according to ER status. METHODS: Immunohistochemical expression of AR and FOXA1 was evaluated on 479 consecutive BC, with complete clinical-pathological and follow up data. Fresh-frozen tissues from 65 cases were available. The expression of AR and FOXA1 with ER was validated using mRNA analyses. Survival and Cox proportional hazard analyses were used to evaluate the relationship between FOXA1, AR and prognosis. RESULTS: Expression of ER, AR and FOXA1 was observed in 78, 60 and 85% of cases respectively. Most AR+ cases (97%) were also FOXA1+. The level of FOXA1 mRNA positively correlated with level of both AR mRNA (r = 0.8975; P < 0.001) and ER mRNA (r = 0.7326; P < 0.001). In ER+ BC, FOXA1 was associated with a good prognosis independently of AR expression in the three subgroups analyzed (FOXA1+/AR+; FOXA1+/AR-; FOXA1−/AR-). Multivariate analyses confirmed that FOXA1 may provide more information than AR in Disease-Free Interval (DFI) of ER+ BC patients. CONCLUSION: Our results suggest that in BC the expression of FOXA1 is directly related to the expression of AR. Despite that, FOXA1 is found as superior predicting marker of recurrences compared to AR in ER+ BC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4624-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-60293702018-07-09 FOXA1 and AR in invasive breast cancer: new findings on their co-expression and impact on prognosis in ER-positive patients Rangel, Nelson Fortunati, Nicoletta Osella-Abate, Simona Annaratone, Laura Isella, Claudio Catalano, Maria Graziella Rinella, Letizia Metovic, Jasna Boldorini, Renzo Balmativola, Davide Ferrando, Pietro Marano, Francesca Cassoni, Paola Sapino, Anna Castellano, Isabella BMC Cancer Research Article BACKGROUND: The role of forkhead-box A1 (FOXA1) and Androgen receptor (AR) in breast cancer (BC) has been extensively studied. However, the prognostic role of their co-expression in Estrogen receptor positive (ER+) BC has not been investigated so far. The aim of the present study was thus to assess the co-expression (protein and mRNA) of FOXA1 and AR in BC patients, in order to evaluate their prognostic impact according to ER status. METHODS: Immunohistochemical expression of AR and FOXA1 was evaluated on 479 consecutive BC, with complete clinical-pathological and follow up data. Fresh-frozen tissues from 65 cases were available. The expression of AR and FOXA1 with ER was validated using mRNA analyses. Survival and Cox proportional hazard analyses were used to evaluate the relationship between FOXA1, AR and prognosis. RESULTS: Expression of ER, AR and FOXA1 was observed in 78, 60 and 85% of cases respectively. Most AR+ cases (97%) were also FOXA1+. The level of FOXA1 mRNA positively correlated with level of both AR mRNA (r = 0.8975; P < 0.001) and ER mRNA (r = 0.7326; P < 0.001). In ER+ BC, FOXA1 was associated with a good prognosis independently of AR expression in the three subgroups analyzed (FOXA1+/AR+; FOXA1+/AR-; FOXA1−/AR-). Multivariate analyses confirmed that FOXA1 may provide more information than AR in Disease-Free Interval (DFI) of ER+ BC patients. CONCLUSION: Our results suggest that in BC the expression of FOXA1 is directly related to the expression of AR. Despite that, FOXA1 is found as superior predicting marker of recurrences compared to AR in ER+ BC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4624-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-03 /pmc/articles/PMC6029370/ /pubmed/29970021 http://dx.doi.org/10.1186/s12885-018-4624-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Rangel, Nelson
Fortunati, Nicoletta
Osella-Abate, Simona
Annaratone, Laura
Isella, Claudio
Catalano, Maria Graziella
Rinella, Letizia
Metovic, Jasna
Boldorini, Renzo
Balmativola, Davide
Ferrando, Pietro
Marano, Francesca
Cassoni, Paola
Sapino, Anna
Castellano, Isabella
FOXA1 and AR in invasive breast cancer: new findings on their co-expression and impact on prognosis in ER-positive patients
title FOXA1 and AR in invasive breast cancer: new findings on their co-expression and impact on prognosis in ER-positive patients
title_full FOXA1 and AR in invasive breast cancer: new findings on their co-expression and impact on prognosis in ER-positive patients
title_fullStr FOXA1 and AR in invasive breast cancer: new findings on their co-expression and impact on prognosis in ER-positive patients
title_full_unstemmed FOXA1 and AR in invasive breast cancer: new findings on their co-expression and impact on prognosis in ER-positive patients
title_short FOXA1 and AR in invasive breast cancer: new findings on their co-expression and impact on prognosis in ER-positive patients
title_sort foxa1 and ar in invasive breast cancer: new findings on their co-expression and impact on prognosis in er-positive patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029370/
https://www.ncbi.nlm.nih.gov/pubmed/29970021
http://dx.doi.org/10.1186/s12885-018-4624-y
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