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Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours - PubMed

Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours

André Albergaria et al. Breast Cancer Res. 2009.

Abstract

Introduction: The expression of additional genes, other than oestrogen receptor (ER), may be important to the hormone-responsive phenotype of breast cancer. Microarray analyses have revealed that forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA-3) are expressed in close association with ERalpha, both encoding for transcription factors with a potential involvement in the ERalpha-mediated action in breast cancer. The purpose of this study was to explore if the expression of FOXA1 and GATA-3 may provide an opportunity to stratify subsets of patients that could have better outcome, among the ERalpha-negative/poor prognosis breast cancer group.

Methods: We evaluate FOXA1 and GATA-3 expression in 249 breast carcinomas by immunohistochemistry, associating it with breast cancer molecular markers, clinicopathological features and patient's survival. The clinicopathological features and immunohistochemical markers of the tumours were compared using the chi-square test and ANOVA. Disease-free survival was analysed through Kaplan-Meier survival curves and Cox regression.

Results: FOXA1 expression was demonstrated in 42% of invasive carcinomas, while GATA-3 was detected in 48% of the cases. FOXA1 expression was inversely associated with tumour size, Nottingham Prognostic Index, histological grade, lymph vascular invasion, lymph node stage and human epidermal growth factor receptor-2 (HER-2) overexpression, while GATA-3 expression showed inverse association with histological grade and HER-2. Both FOXA1 and GATA-3 were directly associated with ERalpha and progesterone receptor. Among FOXA1-positive tumours, 83.1% are comprised in the luminal A subtype, similar to GATA-3 where 87.7% of positive tumours were classified within this molecular subtype. In the subset of ERalpha-negative patients, those who were FOXA1-negative had a 3.61-fold increased risk of breast cancer recurrence when compared with the FOXA1-positive.

Conclusions: FOXA1 was a significant predictor of good outcome in breast cancer, whereas GATA-3 was an important luminal marker. The expression of FOXA1 may be used for risk stratification among ERalpha-negative patients.

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Figures

Figure 1
Figure 1

Immunohistochemistry panel showing differential expression pattern of FOXA1 and GATA-3. An example of luminal A (L1 to L7), basal-like (B1 to B7) and human epidermal growth factor receptor 2 (HER-2)-overexpressing (H1 to H7) invasive breast tumours. Expression of the most commonly used breast cancer markers is also illustrated for comparison with the forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA-3) expression. (L1, B1, H1) Haematoxylin-eosin stainings from each of the selected core cases. (L3, L4) Strong and restricted nuclear expression of FOXA1 and GATA-3 in the normal breast duct (internal control) and in the luminal A invasive tumour (grade II). (B3, B4) Negative expression of FOXA1 and GATA-3 in basal subtype tumour (grade III). (H3, H4) HER-2-overexpressing tumour showing negativity for FOXA1 and GATA-3 expression (grade III). All microscopy images are at 40× magnification. ER, oestrogen receptor; P-CAD, P-cadherin; CK, cytokeratin.

Figure 2
Figure 2

Kaplan–Meier survival curves for disease-free survival. (a) Survival functions for forkhead box A1 (FOXA1) in the whole breast cancer patient series (P < 0.001). (b) Survival functions for GATA binding protein 3 (GATA-3) in the whole breast cancer patient series (P = 0.055). (c) Survival functions for FOXA1 in the oestrogen receptor α-negative breast cancer patient cohort (P = 0.064). (d) Survival functions for GATA-3 in the oestrogen receptor α-negative breast cancer patient cohort (P = 0.488).

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