Spontaneous antibodies against E ngrailed‐2 ( EN 2) protein in patients with prostate cancer

Summary We reported the expression of the homeodomain‐containing transcription factor E ngrailed‐2 ( EN 2) in prostate cancer and showed that the presence of EN 2 protein in the urine was highly predictive of prostate cancer. This study aimed to determine whether patients with prostate cancer have EN 2 autoantibodies, what the prevalence of these antibodies is and whether they are associated with disease stage. The spontaneous immunoglobulin ( Ig)G immune response against EN 2 and for comparison the tumour antigen New York Esophageal Squamous Cell Carcinoma 1 ( NY‐ESO ‐1), were tested by enzyme‐linked immunosorbent assay ( ELISA) in three different cohorts of prostate cancer patients as well as a group of men genetically predisposed to prostate cancer. Thirty‐two of 353 (9·1%) of the SUN cohort representing all stages of prostate cancer demonstrated EN 2 IgG responses, 12 of 107 patients (11·2%) in the advanced prostate cancer patients showed responses, while only four of 121 patients (3·3%) with castrate‐resistant prostate cancer showed EN 2 autoantibodies. No significant responses were found in the predisposed group. Anti‐ EN 2 IgG responses were significantly higher in patients with prostate cancer compared to healthy control males and similarly prevalent to anti‐ NY‐ESO ‐1 responses. While EN 2 autoantibodies are not a useful diagnostic or monitoring tool, EN 2 immunogenicity provides the rationale to pursue studies using EN 2 as an immunotherapeutic target.