Interaction of Upstream Stimulatory Factor 2 and FOXA1 in Breast Cancer.
Rohit K Jain, Rutika Mehta, Payal M Sojitra, Harikrishna Nakshatri, Sunil Badve. Indiana University School of Medicine, Indianapolis
Background: Forkhead box protein A1 (FOXA1), a transcription factor plays an important role in controlling nearly 50% of estrogen receptor target genes and has been deemed as a 'pioneer factor'. In earlier studies it has been demonstrated that FOXA1 is a good prognostic marker that correlates with Luminal subtype A tumors. The Upstream stimulatory factor 2 (USF2), an E-box binding transcription factor has a DNA binding domain similar to FOXA1. Prior studies conducted in prostate cancer have shown direct physical interaction between FOXA1 and USF2. The aim of this study is to understand the relationship of USF2 and FOXA1 in breast cancer.
Design: Expression of USF2 was analyzed on a breast cancer tissue microarray (TMA) using immunohistochemistry (IHC). The TMA consisted of 1 mm tissue cores from 114 breast cancer patients. Data regarding age, tumor type, grade, tumor size, nodal status, ER, PR and HER2 status were available for this cohort. FOXA1 and GATA3 staining was done using previously described methods while for USF2 mouse antihuman monoclonal antibody (Abcam, USA) was used. Both nuclear and cytoloplasmic staining of USF2 was scored using Histoscore method
Results: Mean age of patients and tumor size was 57 years and 3.2 cm respectively. Continuous cytoloplasmic score was positively associated with ER (p= 0.011), PR (p=0.013), GATA3 (p=0.016) and FOXA1 (p=0.007). Continuous nuclear score also positively correlated with ER (p= 0.003), PR (p<0.0001), GATA3 (p=0.004) and FOXA1 (p=0.031).
Conclusions: USF2 appears to be one of the components of FOXA1 transcriptional protein complex. It promises to be a good prognostic marker in breast cancer. Further studies to identify such subsets of patients are warranted.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 12, Wednesday Afternoon