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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number35121
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Oct 7 2016

ASJC Scopus subject areas

  • General

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