[233] Expression of Transcription Factors [FOXA1, GATA-3] in Estrogen Receptor Negative (ER-) and Progesterone Receptor Positive (PR+) Groups: A Single Hormone Receptor Subset Analysis

DF Jones, G Carter, D Gingell, K McManus, M Chivukula. Magee Womens Hospital of UPMC, Pittsburgh, PA

Background: Estrogen receptor (ER) plays a key role in development and influences treatment outcome in breast cancer patients. Ligand binding assays have revealed a small subset of the hormone receptor (HR) category which is single receptor positive. Recently functional interactions between FOXA1 transcription factor of the fork head family and ER are shown to play a critical role in suppressing ER-dependent breast cancer cell growth and tumorigenesis in vivo. This suggests that FOXA1 may be a novel marker that can inhibit and prevent tumor proliferation and development of invasion. Similarly GATA family transcription factors are shown to be highly expressed in the mammary epithelium; exclusively in the luminal epithelial cells. Targeted deletion of GATA-3 leads to profound defects in mammary development and the inability to specify and maintain the luminal cell fate shown in mouse models. In breast cancer, GATA-3 has emerged as a strong predictor of tumor differentiation, ER status, and clinical outcome. The specific aim of this study is to analyze the expression of novel biological transcription markers FOXA1 and GATA-3 in ER-/PR+ breast cancers.
Design: Twenty five (25) cases of the ER-/PR+ group were selected from our archives. Criteria defining the ER-/PR+ group was (1) absent ER expression by two clones and (2) positive for PR expression. Nuclear staining of 10% or more of the tumor cells defined a positive FOXA1 and GATA-3. A cumulative “H score” is derived based on proportionality and intensity scores [H = 0 negative, 1-150 low, 151-250 intermediate, 250-300 high]. All results of ER and PR were confirmed by two clones for both ER {6F11/ SP1} and PR {1A6 and 1E2} on the Benchmark XT according to the FDA protocol. Staining for PR clone 636 was also performed on a DAKO auto stainer and FDA protocol.
Results: Moderate to strong GATA-3 expression was seen in 23 cases (92%; H score mean = 110, range 5-210). On the other hand low FOXA1 expression was seen in 21 (77%; H score mean = 27, range 5-130).
Conclusions: 1. Moderate to strong expression of GATA-3 in seen in up to 92% of ER-/PR+ cases, suggesting the expression of transcription factors in ER- tumors. 2. Expression of FOXA1/GATA-3 in ER-/PR+ cases may play an important role in the hormone responsiveness of these tumors. 3. FOXA1 and GATA-3 may offer new promising targets for therapy in this small, hormone unresponsive group.
Category: Breast

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 62, Tuesday Morning

 

Close Window