Background: Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, PCa recurrence and progression rates during ADT are high. Until now, there has been no evidence regarding when progression begins. This study evaluated the gene expression of intraprostatic androgen receptor (AR) and steroidogenic enzymes in the early stages of ADT. Methods: Prostate tissue samples were taken from PCa patients with urinary retention who received ADT (ADT-PCa; n=10) and were further subgrouped into ADT ≤12 months (n=4) and ADT >12 months (n=6). The ADT-PCa tissues were then compared with BPH (n=12) and primary (no treatment) PCa tissues (n=16). mRNA for gene expression analysis of AR and steroidogenic enzymes was extracted from formalin-fixed paraffin embedded (FFPE) tissues and analyzed by real-time PCR. Protein expression was evaluated by immunohistochemistry with specific antibodies. Results: AR gene expression was higher in the ADT-PCa group than in the BPH or primary PCa group. Both the ADT ≤12 and > 12 months subgroups had significantly higher relative gene expression levels of AR (p<0.01 and 0.03, respectively) than the primary PCa group. In the ADT-PCa group, AR protein expression showed an increasing trend in the ADT ≤12 months subgroup and was significantly elevated in the ADT >12 months subgroup compared with the PCa group (100%; p <0.01). Half (50%) of the patients in the ADT ≤12 months subgroup were found to have upregulation of AR, and one showed upregulation beginning at 3 months of ADT. A trend toward elevated relative gene expression of SRD5A3 was also apparent in the ADT groups. Conclusion: AR and steroidogenic enzymes are upregulated in ADT-PCa patients as early as 3 months, without PSA elevation. Steroidogenic enzymes, particularly SRD5A3, were also upregulated before PSA rose.

Purpose 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 and protein expression of SRD5A1 and SRD5A3 were also found in one patient with 3 months of 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 SRD5A, expression was also upregulated before PSA rises.

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.