Role of Transcription Factors [FOXA1, GATA-3] in Predicting Outcome in (ER+) and (ER-) Ductal Carcinoma-In-Situ (DCIS) Patients with and without Invasive Carcinoma (IC): A Retrospective Subset Analysis
J Picarsic, A Brufsky, G Ahrendt, A Onisko, M Chivukula. Magee Women's Hospital of UPMC, Pittsburgh, PA; UPMC Cancer Institute, Pittsburgh, PA
Background: Estrogen receptor (ER) plays key role in development and influence of treatment outcome in breast cancer patients. The two broad groups of invasive carcinoma (IC) based on ER expression, namely ER(+) and ER(-), are yet to be fully understood in DCIS. Absence of ER has been indicated as a predictor of IC recurrence in DCIS. Recently functional interaction between FOXA1 transcription factor and ER has been shown to play a critical role in suppressing ER-dependent breast cancer cell growth and tumorigenesis in vivo. The GATA family of transcription factors, highly expressed in the mammary epithelium, 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, GATA-3, and established proliferation markers such as MIB-1(Ki-67); and HER2/neu in ER(+) and ER(-) DCIS patients.
Design: Two hundred and ninty-one cases of DCIS were retrieved from our Pathology database, with complete data on 219 cases. The follow-up period from 1988-2009. Recurrence is defined in terms of DCIS or IC. A 10% or more nuclear staining of the tumor cells was considered positive for FOXA1, GATA3, ER, PR. MIB-1 proliferation index (1-10%-low, 11-25%-intermediate, 26-50%-high, >51%-very high); HER-2 is a membrane stain and interpreted as per routine guidelines for IC. Statistical analysis: Fisher's exact test for testing the dependence between clinical outcome (non-recurrence, recurrent-IDC and recurrent -DCIS) for each biomarker with calculation of p-value.
Results: No recurrence was seen in 88% (193/219) cases, 12% (26/219) had recurrence (13 IC, 13 DCIS). FOXA1 and GATA-3 expression is maintained in 98% of ER(-) cases. We are reporting the initial results of biological marker expression in terms of recurrence. A high recurrence is seen with low GATA-3 expression (p=0.78) and low/absent PR (p=0.07).
Conclusions: A strong expression of FOXA 1, GATA-3, low Ki-67 index, and absent Her2 expression are characteristically seen in our ER(+) DCIS group, similar to previously described in IC. However, nearly all of the ER(-) cases expressed FOXA1 and GATA-3 which needs be evaluated further, as these transcription factors may offer new promising targets for therapy.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 63, Tuesday Morning