Higher TRPS-1 Expression Independently Predicts Better Clinical Outcome in ER+ Breast Cancer
Jie Qing Chen, Li Xiao, Yun Wu, Jennifer Litton, Renke Zhou, Xiaoyun Shen, Ausegul A Sahin, Ruth L Katz, Melissa Bondy, James L Murray, Laszlo G Radvanyi. UT MD Anderson Cancer Center, Houston; VA Baylor College of Medicine, Houston
Background: The Trichorhinophalangeal Syndrome-gene (TRPS-1), a novel GATA transcription factor family member, is one of the most prevalent genes expressed in breast cancer based on microarray and immunohistochemistry (IHC) screening. Recent studies have found that TRPS-1 is an EMT inhibitor targeted by miR221/222 in breast cancer (BC). In this study, we developed a new quantitative IHC (qIHC) method to determine whether TRPS-1 may be a clinical prognostic marker in BC patients, especially in early stage ER+ patients receiving anti-hormone therapy alone.
Design: TRPS-1 expression was measured as a Quick Score (QS) derived from the Labeling Index (LI) and Mean Optical Density (MOD) after IHC and applied to 341 Stage I-III BC patients who did not receive preoperative chemotherapy. Nuclear staining and QS ≥4 for TRPS-1 of tumor cells was defined as high expression, while a QS <4 was considered low expression. The association of TRPS-1 with E-cadherin was also assessed in 36 ER+ invasive ductal carcinoma samples. The relationship between TRPS-1 expression and overall survival (OS), disease-free survival (DFS), as well as tumor characteristics and other biomarkers (ER and GATA-3) were examined.
Results: TRPS-1 protein was found to be heterogeneously and widely expressed in the nuclei of ductal epithelial cells. Higher TRPS-1 expression was significantly associated with a number of clinical and pathological characteristics including clinical stage, nodal status, tumor size, Black's Nuclear Grade, ER status, HER2 status and tumor subtype. Univariate and multivariate Cox regression analysis found that high TRPS-1 expression (QS ≥4) significantly associated with improved OS and DFS. Moreover, in early stage (stage I/II) ER+ BC patients receiving anti-hormone therapy alone, higher TRPS-1 expression was significantly associated with prolonged OS and DFS compared to cases with lower TRPS-1 expression (QS <4). In comparing TRPS-1 and ER expression and GATA-3, we found TRPS-1 out-weighed ER and GATA-3 in multivariate analysis as a parameter predicting improved OS and RFS.
Conclusions: The level of TRPS-1 expression can predict clinical outcome in BC patients independently, and may be even a more powerful biomarker than ER for clinical use. The results suggest that TRPS-1 can be used as a marker together with ER, PR and HER2/neu staining, especially to predict the efficiency of anti-hormone therapy. The level of TRPS-1 may be used as a guide to select ER+ BC patients who have lower TRPS-1 expression for more aggressive or alternative therapies to prevent relapse.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 30, Monday Morning