Stability and Prognostic Value of Slug, Sox9 and Sox10 Expression in Breast Cancers Treated with Neoadjuvant Chemotherapy
Cosima Riemenschnitter, Ivett Teleki, Verena Tischler, Wenjun Guo, Zsuzsanna Varga. Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland; Semmelweis University, Budapest, Hungary; Albert Einstein College of Medicine, New York, NY
Background: Expression of transcription factors as Slug and Sox9 was recently used to determine mammary stem cell state. In this study we addressed the prognostic role of Slug, Sox9 and Sox10 expression in neoadjuvant treated primary breast cancer and their correlation to pathological response and overall survival. Furthermore, we tested stability of these markers during chemotherapy.
Design: We analyzed immunohistochemical expression of Slug, Sox9 and Sox10 in tissue microarrays of 96 breast cancers prior to and after neoadjuvant chemotherapy. Expression was evaluated in invasive tumor cells and in tumor stroma and scored as 0, 1+, 2+ 3+. Expression profile prior to and after chemotherapy was correlated to overall survival (Kaplan Meier) and with established clinico-pathological parameter.
Results: Sox9, Sox10 and Slug were expressed in 82-96% of the tumor cells prior to chemotherapy. Slug was expressed in 97% of the cases in tumor stroma before therapy. Change in expression profile after chemotherapy occurred only in Slug expression in tumor cells (decreased from 82 to 51%, p=0.0001, Fisher's exact test). The other markers showed no significant change after chemotherapy. Stromal Sox9 expression (0 to 2+) correlated to better overall survival after chemotherapy (p=0.004) and reached almost statistical significance prior to chemotherapy (p=0.065). There was no correlation between Sox9 and hormone receptor expression. In multivariate analysis, the stromal Sox9 expression after chemotherapy proved to be an independent and better prognostic marker than hormone receptor status. Other clinicopathological parameter (as Her2 status or pathological stage) showed no correlation to the studied markers.
Conclusions: Strong stromal Sox9 expression in breast cancer after chemotherapy was found to bear negative prognostic information and was associated with shortened overall survival.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 25, Wednesday Morning