Research article

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

André Albergaria^1,2 , Joana Paredes² , Bárbara Sousa² , Fernanda Milanezi² , Vítor Carneiro³ , Joana Bastos^4,5 , Sandra Costa¹ , Daniella Vieira⁶ , Nair Lopes² , Eric W Lam⁷ , Nuno Lunet^4,5 and Fernando Schmitt^2,8

¹  Development Domain, Institute of Life and Health Sciences (ICVS), School of Health Sciences of Minho University – Campus de Gualtar, Braga 4710-057, Portugal

²  Cancer Genetics Group, Institute of Molecular Pathology and Immunology of Porto University (IPATIMUP), Rua Dr Roberto Frias s/n, Porto 4200-465, Portugal

³  Department of Pathology of Hospital of Divino Espírito Santo, Rua da Grotinha, Ponta Delgada 9500-370, Portugal

⁴  Department of Hygiene and Epidemiology, University of Porto Medical School, Alameda Prof. Hernâni Monteiro, Porto 4200-319, Portugal

⁵  Institute of Public Health of the University of Porto (ISPUP), Praça Gomes Teixeira s/n, Porto 4099-002, Portugal

⁶  Department of Pathology, Federal University of Santa Catarina, Campus Reitor João David Ferreira Lima, Florianópolis, Santa Catarina CEP 88040-970, Brazil

⁷  Department of Oncology, Cancer Research UK Laboratories, MRC Cyclotron Building, Imperial College of London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK

⁸  Department of Pathology, Medical Faculty of University of Porto, Alameda Prof. Hernâni Monteiro, Porto 4200-319, Portugal

author email corresponding author email

Breast Cancer Research 2009, 11:R40doi:10.1186/bcr2327

Published:	23 June 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 ERα, both encoding for transcription factors with a potential involvement in the ERα-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 ERα-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 ERα 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 ERα-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 ERα-negative patients.