The expressionofandrogenreceptorsplice variant 7 at radical prostatectomy predicts the risk of progression in untreated non-metastatic prostate cancer patients

INTRODUCTION AND OBJECTIVE: Androgen receptor splice variant V7 (AR-V7) was recently detected in circulating tumor cells of castration-resistant prostate cancer (CRPC) patients and its expression correlated with a predictive value in terms of resistance to new generation androgen signaling inhibitors. We retrospectively analyzed whether AR-V7 expression was detectable on prostatic tissues from radical prostatectomy (RP) in an early stage of untreated nonmetastatic PC cases, and whether it could be associated with progression after surgery. METHODS: The expression of AR-V7 and AR-FL (full length) was separately evaluated by immunohistochemistry using a streptavidin-biotin-peroxidase system (UCS Diagnostic) with two antiAR-V7 and anti-AR-FL rabbit monoclonal antibodies (Abcam) on sections from paraffin-embedded tumoral tissues obtained from 56 patients with a histologically proved prostatic adenocarcinoma considered for RP. RESULTS: 56 prostatic tumors, classified on the basis of their clinical risk in low (LR), intermediate (IR) and high (HR) risk, were analyzed with immunohistochemistry for AR-V7: positive expression was found in 24 out of 32 in the HR group, 4 out of 13 in the IR and only in 2 of the 11 LR cases. We found a significant correlation between AR-V7 positive staining and the clinical risk classification (p<0.001), and between AR-V7 positivity and biochemical and radiological progression after surgery (p<0.001). In particular, 17 out of 18 patients with biochemical and radiological progression were ARV7 positive, while 25 out of 26 cases without progression resulted AR-V7 negative. CONCLUSIONS: Although the numbers are too low to draw conclusions, we found that, in a population of untreated and nonmetastatic PC, AR-V7 is detectable by immunohistochemistry, although at low and various rates, in more than 50% of cases. At this early stage, independently to ADT administration, AR-V7 positivity is associated to risk classification and it can predict biochemical and radiological progression after surgery. Validation of our findings in a larger cohort will be relevant for further studies to define a subset of PC cases submitted to RP in which intensification of adjuvant treatments could be indicated.