title: Stability and prognostic value of Slug, Sox9 and Sox10 expression in breast cancers treated with neoadjuvant chemotherapy.
abstract: BACKGROUND
  Expression of transcription-factors as Slug and Sox9 was recently described to determine mammary stem-cell state. Sox10 was previously shown to be present also in breast cancer. Protein overexpression of Slug, Sox9 and Sox10 were associated with poor overall survival and with triple-negative phenotype in breast cancer. In this study we tested the stability of Slug, Sox9 and Sox10 expression during chemotherapy and addressed their prognostic role of in neoadjuvant treated primary breast-cancer and their correlation to pathological-response and overall survival.
  
  
  METHODS
  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 clinico-pathological parameter (as HER2-status or pathological-stage) showed no correlation to the analyzed 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. Slug expression was significantly changed (reduced) in samples after neoadjuvant chemotherapy.
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH 8091 Zurich, Switzerland.
authors.forename: Cosima
authors.initials: C
authors.lastname: Riemenschnitter
authors.affiliation: 1st Department of Pathology & Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Ivett
authors.initials: I
authors.lastname: Teleki
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH 8091 Zurich, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Tischler
authors.affiliation: Ruth L and Davis S Gottesman Institute for Stem Cell Biology and Regenerative Medicine, Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Guo
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH 8091 Zurich, Switzerland ; Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH 8091 Zurich, Switzerland.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Varga
keywords: Breast cancer; Chemotherapy; Prognosis; Stability; Stem cells; Transcription factors