Expression of FOXA1, Estrogen Receptor Associated Transcription Factor, Correlates with Oncotype Dx Recurrence Score
MA Thorat, FO Ademuyiwa, H Nakshatri, S Badve. Indiana University, Indianapolis, IN
Background: FOXA1 is a forkhead family transcription factor expressed in breast cancer cells. We, in addition to others, have reported that FOXA1 expression is associated with good prognosis in breast cancer and it correlates with luminal A subtype. Oncotype Dx assay (ODx) is a commonly used prognostic tool used in ER positive/Node negative breast cancer patients. Recurrence Score (RS) obtained in this test can classify patients in low, intermediate and high risk groups. We investigated whether FOXA1 expression and RS identify the same patient population and whether its expression can serve as a cheaper surrogate for ODx.
Design: We selected 130 cases from Indiana University affiliated hospitals in which ODx assay was performed between years 2005 to 2008. Blocks on which ODx assay was performed were available in 79 cases. IHC was performed on the same block using FOXA1 antibody sc-6553 (Santa Cruz Biotechnology). Briefly, 4 m sections after hydration and antigen retrieval were incubated with goat-anti-human FOXA1 antibody (1:250). The reaction was visualized with anti-goat HRP polymer conjugate (Invitrogen) using DAB plus (Dako) and haematoxylin QS (Vector Laboratories, Burlingame, CA, USA) counterstain. The specificity of staining was verified using non-immune goat serum and PBS controls. Percentage (P) and intensity (I) of nuclear expression were multiplied to generate numerical score (S=P x I). A score of more than 30 is considered positive. Data were analyzed using SPSS 16.0 software.
Results: All patients (n=79) in the study were ER positive and node negative. Patient characteristics are described in table 1. FOXA1 expression correlated negatively with RS (p=0.002) and tumor grade (p=0.004) and with tumor type; higher expression in lobular compared to ductal cancers (p<0.0009). RS also correlated with positively with grade (p=0.037) and tumor type, higher score in ductal cancers (p=0.047). Correlation between FOXA1 expression and RS remained significant even after adjusting for tumor type (p=0.003) or grade (p=0.031).
Conclusions: FOXA1 expression correlates inversely with RS and identifies the same group of patients. Both these prognostic markers aim to identify low risk ER positive node negative patients who can be spared of toxic chemotherapy; these markers can potentially be used interchangeably in clinic if further validation studies confirm our findings.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 20, Wednesday Afternoon