Millican-Slater, RA, Sayers, CD, Hanby, AM et al. (1 more author) (2016) Expression of phosphorylated eIF4E-binding protein 1, but not of eIF4E itself, predicts survival in male breast cancer. British Journal of Cancer, 115 (3). pp. 339-345. ISSN 0007-0920
Abstract
Background: Male breast cancer is rare and treatment is based on data from females. High expression/activity of eukaryotic initiation factor 4E (eIF4E) denotes a poor prognosis in female breast cancer, and the eIF4E pathway has been targeted therapeutically. eIF4E activity in female breast cancer is deregulated by eIF4E over-expression and by phosphorylation of its binding protein, 4E-BP1, which relieves inhibitory association between eIF4E and 4E-BP1. The relevance of the eIF4E pathway in male breast cancer is unknown. Methods: We have assessed expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 (p4E-BP1) using immunohistochemistry in a large cohort of male breast cancers (n=337) and have examined correlations with prognostic factors and survival. Results: Neither eIF4E expression or estimated eIF4E activity were associated with prognosis. However, a highly significant correlation was found between p4E-BP1 expression and disease-free survival, linking any detectable p4E-BP1 with poor survival (univariate log rank p=0.001; multivariate HR 8.8, p=0.0001). Conclusions: Our data provide no support for direct therapeutic targeting of eIF4E in male breast cancer, unlike in females. However, as p4E-BP1 gives powerful prognostic insights that are unrelated to eIF4E function, p4E-BP1 may identify male breast cancers potentially suitable for therapies directed at the upstream kinase, mTOR.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Cancer Research UK. All rights reserved. This is an author produced version of a paper published in British Journal of Cancer. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | male breast cancer, translational regulation, predictive markers |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Molecular Gastroenterology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 02 Jun 2016 10:26 |
Last Modified: | 14 Dec 2016 08:18 |
Published Version: | http://dx.doi.org/10.1038/bjc.2016.178 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/bjc.2016.178 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:100407 |