Abstract
IntroductionThe 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.MethodsFollowing 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.ResultsSRAP 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).ConclusionsOur 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.
Highlights
Introduction The steroid receptorRNA activator is a functional RNA suspected to participate in the mechanisms underlying breast tumor progression
Our data suggest that steroid receptor RNA activator protein (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
Anti-SRAP antibody validation The ability of the 743A anti-SRAP antibody (Bethyl, Montgomery, TX, USA) to recognize SRAP was first assessed by western blot analysis of total protein extracted from Michigan Cancer Foundation (MCF)-7 breast cancer cells, previously shown to express this protein [15,16,17]
Summary
Introduction The steroid receptorRNA activator is a functional RNA suspected to participate in the mechanisms underlying breast tumor progression. Growth receptor (HER)-2, which is over-expressed in about 25% of breast cancers and is associated with a more aggressive disease and a poorer outcome, has been used as a prognostic and predictive marker [3] Recent approaches such as gene profiling and tissue micro-arrays (TMAs) have increased our ability to identify new potential markers, and to rapidly test their potential validity [4,5]. The more such molecules are identified, the higher become the odds of finding the optimal combination of markers allowing the determination of an 'ideal' treatment for any given patient [6]
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