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01-08-2008 | Preclinical Study

The prognostic significance of steroid receptor co-regulators in breast cancer: co-repressor NCOR2/SMRT is an independent indicator of poor outcome

Authors: Andrew R. Green, Claire Burney, Christopher J. Granger, E. Claire Paish, Somaia El-Sheikh, Emad A. Rakha, Desmond G. Powe, R. Douglas Macmillan, Ian O. Ellis, Eleni Stylianou

Published in: Breast Cancer Research and Treatment | Issue 3/2008

Abstract

Background

Advances in understanding the molecular basis of breast cancer has necessitated a definition of improved indicators of prognosis that are central to the underlying cancer biology and that reflect the heterogeneous nature of the disease. This study investigates the pattern of expression of the steroid receptor co-regulators NCOA1/SRC1, NCOA3/RAC3, NCOR2/SMRT, and CBP/p300 in breast cancer. The aims were to identify whether their expression was related to patient outcome, their relationships to known prognostic factors and to provide a basis for further research into the mechanistic significance of such associations.

Methods

The protein levels of steroid receptor co-regulators were assessed by immunohistochemistry in a large well-characterised series of breast carcinomas prepared as tissue microarrays. Relationships between these targets, other clinicopathological variables and patients’ outcome were examined.

Results

NCOR2/SMRT was an independent prognostic indicator of overall patient survival (OS) and disease free interval (DFI) and was significantly correlated with distant metastases and local recurrence whereas tumours expressing NCOA1/SRC1 had a significantly longer OS and DFI. There were also significant correlations between co-regulator expression of NCOA1/SRC1, CBP/p300 and NCOA3/RAC3, which were associated with lower tumour grade. NCOA1/SRC1 was also correlated with smaller tumour size. Furthermore, the co-activators had a significant association with steroid receptors, particularly ERα.

Conclusions

NCOR2/SMRT is associated with poor patient outcome, independent of other prognostic factors. In contrast, steroid receptor co-activator expression is generally associated with a good prognosis. Further investigations are needed to establish the mechanisms of these links between the steroid receptor co-regulator system and patient outcome.

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Title: The prognostic significance of steroid receptor co-regulators in breast cancer: co-repressor NCOR2/SMRT is an independent indicator of poor outcome
Authors: Andrew R. Green
Claire Burney
Christopher J. Granger
E. Claire Paish
Somaia El-Sheikh
Emad A. Rakha
Desmond G. Powe
R. Douglas Macmillan
Ian O. Ellis
Eleni Stylianou
Publication date: 01-08-2008
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2008
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-007-9737-y

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