Abstract
IntroductionThe 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.MethodsWe 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.ResultsFOXA1 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.ConclusionsFOXA1 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.
Highlights
The expression of additional genes, other than oestrogen receptor (ER), may be important to the hormoneresponsive phenotype of breast cancer
forkhead box A1 (FOXA1) expression was demonstrated in 42% of invasive carcinomas, while GATA binding protein 3 (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 GATA3 expression showed inverse association with histological grade and HER-2
Summary
The expression of additional genes, other than oestrogen receptor (ER), may be important to the hormoneresponsive phenotype of breast cancer. The molecular classification of breast cancers distinguishes three major subtypes: the ER-positive/luminal-like subtype, a gene expression cluster characteristic of the luminal cells and anchored by a cluster of transcription factors that include ER; the basal-like subtype, comprising tumours that express basal cell markers (namely keratin 5, keratin 14, integrin β4 and laminin); and the human epidermal growth factor receptor-2 (HER-2)-overexpressing subtype, usually associated with gene amplification of the HER-2 proto-oncogene and high expression of several genes in the ERBB2 amplicon at 17q22.24 [4,5,8] These studies have largely contributed to understanding the complex behaviour of certain types of breast cancer, including the ones that respond better to endocrine therapies, regardless of ER expression
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