Early upregulation of AR and steroidogenesis enzyme expressions after 3 months of androgen-deprivation therapy.

Abstract

Background: Androgen-Deprivation Therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, there is a high recurrence or progression rate during ADT. Until now, there is no evidence on when the progression starts. This study would like to evaluate the early response of intraprostatic androgen receptor (AR) and steroidogenic enzyme gene expressions in ADT.Methods: Prostate tissue samples were taken from PCa patients with urinary retention, who had ADT (ADT- PCa; n=10), and further grouped into ≤12 months (n=4) and ADT >12 months (n=6). ADT-PCa group were then compared with BPH (n=12) and primary (no treatment) PCa tissues (n=16). AR and steroidogenic enzyme genes were extracted from Formalin Fixed Paraffin embedded (FFPE) tissues and analysed using rtPCR. Protein expressions were evaluated by immunohistochemistry of specific antibodies. Results: AR gene expression was found higher in ADT-PCa group compared to BPH and primary PCa. Both ADT ≤12 and > 12 months subgroups had significantly higher relative gene expression of AR (p 0.01 and 0.03) compared to primary PCa. AR protein expression in ADT-PCa group showed an increase trend in ADT ≤12 months subgroup and a significantly elevated expression AR protein in ADT >12 months subgroup compared with PCa (100%; p <0.01). Half (50%) of ADT ≤12 months patients were found to have upregulation of AR, and one undergone upregulation from only 3 months of ADT. A trend of elevating relative gene expression of SRD5A3 were also found within the groups given ADT. Conclusion: There are upregulation of AR and steroidogenic enzymes in ADT-PCa patients, as early as 3 months without showing PSA elevation. Steroidogenic enzyme, especially SRD5A3 expression was also showing upregulation before PSA rises.