Quantitative immunohistochemical analysis and prognostic significance of TRPS-1, a new GATA transcription factor family member, in breast cancer

The trichorhinophalangeal syndrome 1 (TRPS-1) gene is a novel GATA transcription factor family member. Previously, using a gene expression profiling and immuno- histochemistry (IHC) screen, we identified TRPS-1 as a highly prevalent gene in breast cancer (BC), expressed in >90% of estrogen receptor alpha (ERα) ⁺ and ERα ^- BC subtypes. TRPS-1 was also shown to be expressed in prostate cancer where it was shown to play a proapoptotic function during androgen withdrawal possibly through regulating antioxidant metabolism. The role of TRPS-1 and its prognostic significance in hormone-dependent and hormone-independent BC however is not known. In this study, we developed a new quantitative IHC (qIHC) method to further study TRPS-1 as a marker and possible prognostic indicator in BC. By using this method, a quantitative parameter for TRPS-1 expression called a quick score (QS) was derived from the measured labeling index and mean optical density after IHC and applied to a set of 152 stage II/III BC patients from 1993 to 2006 who did not receive preoperative chemotherapy. Associations between QS and tumor characteristics were evaluated using the Kruskal-Wallis test. A wide range of TRPS-1 QS was found among the sample set with higher TRPS-1 QS significantly associated with tumor ERα (p=0.023 for QS and p=0.028 for Allred score), progesterone receptor (p= 0.009), and GATA-3 (p<0.0001). TRPS-1 QS was also positively associated with HER2 status (p=0.026). Further analysis of different ductal structures in ten BC cases revealed that TRPS-1 expression was expressed at low levels in the remaining normal ducts and in areas of usual ductal hyperplasia but showed marked increase in expression in ductal carcinoma in situ and invasive carcinoma lesions in the tissue. An analysis of TRPS-1 expression in association with overall survival in the 152 stage II/III sample set also revealed that TRPS-1 QS (≥4.0) was significantly associated with improved survival (p=0.0165). Patients with TRPS-1 QS <4 had a hazard ratio of 2 (p=0.019) after univariate Cox proportional hazards analysis. In summary, this new qIHC approach was found to reveal critical differences in TRPS-1 expression in primary BC samples and found that it is a promising prognostic marker that should be further evaluated as a possible tumor suppressor gene facilitating improved survival in different subtypes of BC.