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

Anna Di Benedetto; Marcella Mottolese; Francesca Sperati; Cristiana Ercolani; Luigi Di Lauro; Laura Pizzuti; Patrizia Vici; Irene Terrenato; Abeer M Shaaban; Sreekumar Sundara-Rajan; Matthew P Humphries; Maddalena Barba; Valerie Speirs; Ruggero De Maria; Marcello Maugeri-Saccà

doi:10.1038/srep35121

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

Anna Di Benedetto, Marcella Mottolese, Francesca Sperati, Cristiana Ercolani, Luigi Di Lauro, Laura Pizzuti, Patrizia Vici, Irene Terrenato, Abeer M Shaaban, Sreekumar Sundara-Rajan, Matthew P Humphries, Maddalena Barba, Valerie Speirs, Ruggero De Maria, Marcello Maugeri-Saccà

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Abstract

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.

Original language	English
Article number	35121
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep35121
Publication status	Published - 7 Oct 2016

Keywords

Adaptor Proteins, Signal Transducing
Adult
Aged
Aged, 80 and over
Breast Neoplasms, Male
Cholesterol
Gene Expression Regulation, Neoplastic
Humans
Hydroxymethylglutaryl CoA Reductases
Intracellular Signaling Peptides and Proteins
Male
Middle Aged
Phosphoproteins
Protein-Serine-Threonine Kinases
Receptors, Androgen
Receptors, Estrogen
Receptors, Progesterone
Retrospective Studies
Treatment Outcome
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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HMG-CoAR expression in male breast cancer
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Di Benedetto, A., Mottolese, M., Sperati, F., Ercolani, C., Di Lauro, L., Pizzuti, L., Vici, P., Terrenato, I., Shaaban, A. M., Sundara-Rajan, S., Humphries, M. P., Barba, M., Speirs, V., De Maria, R., & Maugeri-Saccà, M. (2016). HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes. Scientific Reports, 6, [35121]. https://doi.org/10.1038/srep35121

Di Benedetto, A, Mottolese, M, Sperati, F, Ercolani, C, Di Lauro, L, Pizzuti, L, Vici, P, Terrenato, I, Shaaban, AM, Sundara-Rajan, S, Humphries, MP, Barba, M, Speirs, V, De Maria, R & Maugeri-Saccà, M 2016, 'HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes', Scientific Reports, vol. 6, 35121. https://doi.org/10.1038/srep35121

@article{1252e23ba3184f26977282f4129f7e06,

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

abstract = "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.",

keywords = "Adaptor Proteins, Signal Transducing, Adult, Aged, Aged, 80 and over, Breast Neoplasms, Male, Cholesterol, Gene Expression Regulation, Neoplastic, Humans, Hydroxymethylglutaryl CoA Reductases, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Phosphoproteins, Protein-Serine-Threonine Kinases, Receptors, Androgen, Receptors, Estrogen, Receptors, Progesterone, Retrospective Studies, Treatment Outcome, Journal Article",

author = "{Di Benedetto}, Anna and Marcella Mottolese and Francesca Sperati and Cristiana Ercolani and {Di Lauro}, Luigi and Laura Pizzuti and Patrizia Vici and Irene Terrenato and Shaaban, {Abeer M} and Sreekumar Sundara-Rajan and Humphries, {Matthew P} and Maddalena Barba and Valerie Speirs and {De Maria}, Ruggero and Marcello Maugeri-Sacc{\`a}",

note = "We thank members of the Male Breast Cancer Consortium for kindly contributing cases. We thank Tania Merlino for technical assistance. ",

year = "2016",

month = oct,

day = "7",

doi = "10.1038/srep35121",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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TY - JOUR

T1 - HMG-CoAR expression in male breast cancer

T2 - relationship with hormone receptors, Hippo transducers and survival outcomes

AU - Di Benedetto, Anna

AU - Mottolese, Marcella

AU - Sperati, Francesca

AU - Ercolani, Cristiana

AU - Di Lauro, Luigi

AU - Pizzuti, Laura

AU - Vici, Patrizia

AU - Terrenato, Irene

AU - Shaaban, Abeer M

AU - Sundara-Rajan, Sreekumar

AU - Humphries, Matthew P

AU - Barba, Maddalena

AU - Speirs, Valerie

AU - De Maria, Ruggero

AU - Maugeri-Saccà, Marcello

N1 - We thank members of the Male Breast Cancer Consortium for kindly contributing cases. We thank Tania Merlino for technical assistance.

PY - 2016/10/7

Y1 - 2016/10/7

N2 - 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.

AB - 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.

KW - Adaptor Proteins, Signal Transducing

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Breast Neoplasms, Male

KW - Cholesterol

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Hydroxymethylglutaryl CoA Reductases

KW - Intracellular Signaling Peptides and Proteins

KW - Male

KW - Middle Aged

KW - Phosphoproteins

KW - Protein-Serine-Threonine Kinases

KW - Receptors, Androgen

KW - Receptors, Estrogen

KW - Receptors, Progesterone

KW - Retrospective Studies

KW - Treatment Outcome

KW - Journal Article

U2 - 10.1038/srep35121

DO - 10.1038/srep35121

M3 - Article

C2 - 27713571

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 35121

ER -

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

Abstract

Keywords

UN SDGs

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