Transcript levels of androgen receptor variant AR-V1 or AR-V7 do not predict recurrence in patients with prostate cancer at indeterminate risk for progression.

ABSTRACT

PURPOSE: AR-V7, a ligand independent splice variant of androgen receptor, may support the growth of castration resistant prostate cancer and have prognostic value. Another variant, AR-V1, interferes with AR-V7 activity. We investigated whether AR-V7 or V1 expression would predict biochemical recurrence in men at indeterminate (about 50%) risk for progression following radical prostatectomy. MATERIALS AND METHODS: AR-V7 and V1 transcripts in a mixed grade cohort of 53 men in whom cancer contained 30% to 70% Gleason grade 4/5 and in a grade 3 only cohort of 52 were measured using a branched chain DNA assay. Spearman rank correlations of the transcripts, and histomorphological and clinical variables were determined. AR-V7 and V1 levels were assessed as determinants of recurrence in the mixed grade cohort by logistic regression and survival analysis. The impact of TMPRSS2-ERG gene fusion on prognosis was also evaluated. RESULTS: Neither AR-V7 nor V1 levels in grade 3 or 4/5 cancer in the mixed grade cohort were associated with recurrence or time to recurrence. However, AR-V7 and V1 inversely correlated with serum prostate specific antigen and positively correlated with age. The AR-V1 level in grade 3 cancer in the grade 3 only cohort was higher than in grade 3 or grade 4/5 components of mixed grade cancer. TMPRSS2-ERG fusion was not associated with AR-V7, AR-V1 or recurrence but it was associated with the percent of grade 4/5 cancer. CONCLUSIONS: The AR-V1 or V7 transcript level does not predict recurrence in patients with high grade prostate cancer at indeterminate risk for progression. Grade 3 cancer in mixed grade tumors may differ from 100% grade 3 cancer, at least in AR-V1 expression.