Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours.
BACKGROUND
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.
Albergaria
André
A
Development Domain, Institute of Life and Health Sciences (ICVS), School of Health Sciences of Minho University, Campus de Gualtar, Braga, Portugal. aalbergaria@ipatimup.pt
Paredes
Joana
J
Sousa
Bárbara
B
Milanezi
Fernanda
F
Carneiro
Vítor
V
Bastos
Joana
J
Costa
Sandra
S
Vieira
Daniella
D
Lopes
Nair
N
Lam
Eric W
EW
Lunet
Nuno
N
Schmitt
Fernando
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D050990:GATA3 Transcription Factor / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000378:metabolism*; D016896:Treatment Outcome
C496499:FOXA1 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D011960:Receptors, Estrogen