HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes

HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes

Male breast cancer (MBC) is a rare hormone-driven disease often associated with obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR regulates the oncogenic Hippo transducers TAZ/YAP whose expression...

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Main Authors: Di Benedetto, Anna, Mottolese, Marcella, Sperati, Francesca, Ercolani, Cristiana, Di Lauro, Luigi, Pizzuti, Laura, Vici, Patrizia, Terrenato, Irene, Shaaban, Abeer M., Sundara-Rajan, Sreekumar, Humphries, Matthew P., Barba, Maddalena, Speirs, Valerie, De Maria, Ruggero, Maugeri-Saccà, Marcello
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054365/
id pubmed-5054365
recordtype oai_dc
spelling pubmed-50543652016-10-19 HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes Di Benedetto, Anna Mottolese, Marcella Sperati, Francesca Ercolani, Cristiana Di Lauro, Luigi Pizzuti, Laura Vici, Patrizia Terrenato, Irene Shaaban, Abeer M. Sundara-Rajan, Sreekumar Humphries, Matthew P. Barba, Maddalena Speirs, Valerie De Maria, Ruggero Maugeri-Saccà, Marcello Article Male breast cancer (MBC) is a rare hormone-driven disease often associated with obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR regulates the oncogenic Hippo transducers TAZ/YAP whose expression was previously associated with shorter survival in MBC. 225 MBC samples were immunostained for HMG-CoAR and 124 were considered eligible for exploring its relationship with hormone receptors (ER, PgR, AR), Hippo transducers and survival outcomes. HMG-CoAR was positively associated with the expression of hormone receptors (ER, PgR, AR) and Hippo transducers. Overall survival was longer in patients with HMG-CoAR-positive tumors compared with their negative counterparts (p = 0.031). Five- and 10-year survival outcomes were better in patients whose tumors expressed HMG-CoAR (p = 0.044 and p = 0.043). Uni- and multivariate analyses for 10-year survival suggested that HMG-CoAR expression is a protective factor (HR 0.50, 95% CI: 0.25–0.99, p = 0.048 and HR 0.53, 95% CI: 0.26–1.07, p = 0.078). Results were confirmed in a sensitivity analysis by excluding uncommon histotypes (multivariate Cox: HR 0.45, 95% CI: 0.21–0.97, p = 0.043). A positive relationship emerged between HMG-CoAR, hormone receptors and TAZ/YAP, suggesting a connection between the mevalonate pathway, the hormonal milieu and Hippo in MBC. Moreover, HMG-CoAR expression may be a favorable prognostic indicator. Nature Publishing Group 2016-10-07 /pmc/articles/PMC5054365/ /pubmed/27713571 http://dx.doi.org/10.1038/srep35121 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Di Benedetto, Anna
Mottolese, Marcella
Sperati, Francesca
Ercolani, Cristiana
Di Lauro, Luigi
Pizzuti, Laura
Vici, Patrizia
Terrenato, Irene
Shaaban, Abeer M.
Sundara-Rajan, Sreekumar
Humphries, Matthew P.
Barba, Maddalena
Speirs, Valerie
De Maria, Ruggero
Maugeri-Saccà, Marcello
spellingShingle Di Benedetto, Anna
Mottolese, Marcella
Sperati, Francesca
Ercolani, Cristiana
Di Lauro, Luigi
Pizzuti, Laura
Vici, Patrizia
Terrenato, Irene
Shaaban, Abeer M.
Sundara-Rajan, Sreekumar
Humphries, Matthew P.
Barba, Maddalena
Speirs, Valerie
De Maria, Ruggero
Maugeri-Saccà, Marcello
HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes
author_facet Di Benedetto, Anna
Mottolese, Marcella
Sperati, Francesca
Ercolani, Cristiana
Di Lauro, Luigi
Pizzuti, Laura
Vici, Patrizia
Terrenato, Irene
Shaaban, Abeer M.
Sundara-Rajan, Sreekumar
Humphries, Matthew P.
Barba, Maddalena
Speirs, Valerie
De Maria, Ruggero
Maugeri-Saccà, Marcello
author_sort Di Benedetto, Anna
title HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes
title_short HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes
title_full HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes
title_fullStr HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes
title_full_unstemmed HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes
title_sort hmg-coar expression in male breast cancer: relationship with hormone receptors, hippo transducers and survival outcomes
description Male breast cancer (MBC) is a rare hormone-driven disease often associated with obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR regulates the oncogenic Hippo transducers TAZ/YAP whose expression was previously associated with shorter survival in MBC. 225 MBC samples were immunostained for HMG-CoAR and 124 were considered eligible for exploring its relationship with hormone receptors (ER, PgR, AR), Hippo transducers and survival outcomes. HMG-CoAR was positively associated with the expression of hormone receptors (ER, PgR, AR) and Hippo transducers. Overall survival was longer in patients with HMG-CoAR-positive tumors compared with their negative counterparts (p = 0.031). Five- and 10-year survival outcomes were better in patients whose tumors expressed HMG-CoAR (p = 0.044 and p = 0.043). Uni- and multivariate analyses for 10-year survival suggested that HMG-CoAR expression is a protective factor (HR 0.50, 95% CI: 0.25–0.99, p = 0.048 and HR 0.53, 95% CI: 0.26–1.07, p = 0.078). Results were confirmed in a sensitivity analysis by excluding uncommon histotypes (multivariate Cox: HR 0.45, 95% CI: 0.21–0.97, p = 0.043). A positive relationship emerged between HMG-CoAR, hormone receptors and TAZ/YAP, suggesting a connection between the mevalonate pathway, the hormonal milieu and Hippo in MBC. Moreover, HMG-CoAR expression may be a favorable prognostic indicator.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054365/
_version_ 1613676213972238336

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