Research article

Steroid Receptor RNA Activator Protein (SRAP): a potential new prognostic marker for estrogen receptor-positive/node-negative/younger breast cancer patients

Yi Yan^1,2†, George P Skliris^1,2†, Carla Penner², Shilpa Chooniedass-Kothari^1,2, Charlton Cooper², Zoann Nugent¹, Anne Blanchard³, Peter H Watson⁴, Yvonne Myal³, Leigh C Murphy^1,2 and Etienne Leygue^1,2*

• * Corresponding author: Etienne Leygue eleygue@cc.umanitoba.ca

• † Equal contributors

Author Affiliations

¹ Manitoba Institute of Cell Biology, 675 McDermot Avenue, R3E0V9, Winnipeg, Manitoba, Canada

² Department of Biochemistry and Medical Genetics, University of Manitoba, 770 Bannatyne Avenue, R3E0W3, Winnipeg, Manitoba, Canada

³ Department of Physiology, University of Manitoba, 770 Bannatyne Avenue, R3E0W3, Winnipeg, Manitoba, Canada

⁴ BC Cancer Agency's Trev & Joyce Deeley Research Centre, 2410 Lee Avenue, V8R 6V5, Victoria, BC, Canada

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Breast Cancer Research 2009, 11:R67 doi:10.1186/bcr2359

Published: 9 September 2009

Abstract

Introduction

The steroid receptor RNA activator is a functional RNA suspected to participate in the mechanisms underlying breast tumor progression. This RNA is also able to encode for a protein, Steroid Receptor RNA Activator Protein (SRAP), whose exact function remains to be determined. Our aim was to assess, in a large breast cancer cohort, whether levels of this protein could be associated with outcome or established clinical parameters.

Methods

Following antibody validation, SRAP expression was assessed by tissue-microarray (TMA) analysis of 372 breast tumors. Clinical follow-up and parameters such as steroid receptor and node status were available for all the corresponding cases. Immunohistochemical scores were independently determined by three investigators and averaged. Statistical analyses were performed using standard univariate and multivariate tests.

Results

SRAP levels were significantly (Mann-Whitney rank sum test, P < 0.05) higher in estrogen receptor-alpha positive (ER+, n = 271), in progesterone receptor positive (PR+, n = 257) and in older patients (age > 64 years, n = 182). When considering ER+ tumors, PR+ tumors, or younger patients (≤ 64 years), cases with high SRAP expression had a significantly (Mantel-Cox test, P < 0.05) worse breast cancer specific survival (BCSS) than those with low SRAP levels. SRAP also appeared as a very powerful indicator of poor prognostic for BCSS in the subset of ER+, node negative and young breast cancer patients (Cox regression analysis, n = 60, BCSS Hazard Ratio = 8.61, P < 0.006).

Conclusions

Our data suggest that SRAP levels might provide additional information on potential risk of recurrence and negative outcome in a specific set of patients with otherwise good prognosis when considering only estrogen receptor and nodal status.