Forkhead-box A1 (FOXA1) expression in breast cancer and its prognostic significance

Habashy, Hany Onsy; Powe, Desmond G.; Rakha, Emad A.; Ball, Graham; Paish, Claire; Gee, Julia; Nicholson, Robert I.; Ellis, Ian O.

doi:10.1016/j.ejca.2008.04.020

« Previous Next »European Journal of Cancer
Volume 44, Issue 11 , Pages 1541-1551, July 2008

Forkhead-box A1 (FOXA1) expression in breast cancer and its prognostic significance

Hany Onsy Habashy
- Department of Histopathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
- Department of Histopathology, Faculty of Medicine, Mansoura University, Egypt
Desmond G. Powe
- Department of Histopathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
Emad A. Rakha
- Department of Histopathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
Graham Ball
- Division of Life Sciences, Nottingham Trent University, Nottingham, UK
Claire Paish
- Department of Histopathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
Julia Gee
- Welsh School of Pharmacy, Cardiff University, Cardiff, UK
Robert I. Nicholson
- Welsh School of Pharmacy, Cardiff University, Cardiff, UK
Ian O. Ellis
- Department of Histopathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
- Corresponding author: Tel.: +44 0 115 9691169; fax: +44 0 115 9627768.

Received 19 February 2008; received in revised form 15 April 2008; accepted 25 April 2008. published online 06 June 2008.

Abstract

The forkhead-box A1 (FOXA1) controls downstream transcription of oestrogen receptor (ER)-regulated genes. In this study, the biological and prognostic value of FOXA1 expression was assessed immunohistochemically in a large and well-characterised series of invasive breast carcinoma with a long term follow-up using tissue microarray. FOXA1 expression was associated with steroid hormone receptors (ERα, PgR and AR), other variables of good prognosis such as smaller tumour size, lower histological grade, luminal cytokeratins (CK18 and CK7/8), BRCA1 and E-cadherin. Its expression showed an inverse relation with basal CKs (CK14 and CK5/6) and P-cadherin. We found an association between high FOXA1 expression and a better survival in the whole series however; multivariate analysis showed that FOXA1 was not an independent prognostic marker.

In conclusion, our results show that FOXA1 protein is associated with markers of good prognosis supporting its role as a growth repressor in breast cancer. In this series, FOXA1 was found not to be of an independent prognostic significance in breast cancer and as such its immunohistochemical assessment alone does not appear to have relevance in routine practice to stratify ER-positive (luminal-like) tumours into clinically significant subgroups.

Keywords: Breast carcinoma, FOXA1, Oestrogen receptor, Prognosis