High-level expression of forkhead-box protein A1 in metastatic prostate cancer.

Overview

AIMS: Expression of forkhead-box protein A1 (FOXA1), a transcription factor important for normal development of the prostate gland, is thought to be controlled by steroid hormones and GATA3. The aim of this study was to investigate the expression and potential role of FOXA1 and GATA3 transcription factors as prognostic factors in prostate cancer. METHODS AND RESULTS: Expression of FOXA1, GATA3 and androgen receptor (AR) was retrospectively analysed by immunohistochemistry in a series of 80 primary tumours and 28 metastatic prostate cancers, including 15 matched paired samples. Nuclear AR expression did not significantly differ between primary and metastatic tumours. High-level nuclear FOXA1 expression was seen in 19% of primary and 89% of metastatic tumours (P < 0.0001). FOXA1 expression correlated positively with tumour size, extraprostatic extension, angiolymphatic invasion, AR and lymph node metastases at diagnosis, but did not correlate with age, T stage, Gleason score, presence of prostatic intraepithelial neoplasia or multifocality, seminal vesicle or perineural invasion, or surgical excision margin status. Expression of GATA3 was not seen in either normal epithelium or tumour. CONCLUSIONS: Our preliminary analyses suggest that high-level FOXA1 expression is associated with the development of metastatic prostate cancer. If these data are confirmed, FOXA1 expression could be used to classify patients at higher risk for metastases.