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

Background

Advances in the understanding of the molecular basis of breast cancer has necessitated a definition of more sensitive and specific indicators of prognosis that are central to the underlying cancer biology and that reflect the complicated and heterogeneous nature of the disease. The present study investigates the pattern of expression of the steroid receptor coregulators 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 to investigate the mechanistic significance of such associations.

Method

The protein levels of steroid receptor coregulators were assessed using 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

The most important finding was that NCOR2/SMRT was an independent prognostic indicator of overall patient survival and the disease-free interval and was significantly correlated with distant metastases and local recurrence, whereas tumours expressing NCOA1/SRC1 had significantly longer overall patient survival and disease-free interval. There were also significant correlations between coregulator expression of NCOA1/SRC1, CBP/p300 and NCOA3/RAC3 that were associated with lower tumour grade. NCOA1/SRC1 was also correlated with smaller tumour size. Furthermore, the coactivators had a significant association with steroid receptors, particularly estrogen receptor alpha.

Conclusion

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