FOXA1 expression is a strong independent predictor of early PSA recurrence in ERG negative prostate cancers treated by radical prostatectomy.

FOXA1 (Fork-head box protein A1, HNF-3a) is a transcription factor involved in androgen signaling with relevance for lineage-specific gene expression of the prostate. The expression was analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with tumor phenotype, biochemical recurrence, androgen receptor expression, ETS-related gene (ERG) status and other recurrent genomic alterations. FOXA1 expression was detectable in 97.6% of 8227 interpretable cancers and considered strong in 28.5%, moderate in 46.2% and weak in 22.9% of cases. High FOXA1 expression was associated with TMPRSS2:ERG rearrangement and ERG expression (P < 0.0001). High FOXA1 expression was linked to high Gleason grade, advanced pathological tumor (pT) stage and early PSA recurrence in ERG negative cancers (P < 0.0001), while these associations were either weak or absent in ERG positive cancers. In ERG negative cancers, the prognostic role of FOXA1 expression was independent of Gleason grade, pathological tumor stage, lymph node stage, surgical margin status and preoperative PSA. Independent prognostic value became even more evident if the analysis was limited to preoperatively available features such as biopsy Gleason grade, preoperative PSA, cT stage and FOXA1 expression (P < 0.0001). Within ERG negative cancers, FOXA1 expression was also strongly associated with PTEN and 5q21 deletions (P < 0.0001). High expression of FOXA1 is an independent prognostic parameter in ERG negative prostate cancer. Thus, FOXA1 measurement might provide clinically useful information in prostate cancer.