ORIGINAL ARTICLES

Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer

K Wako^1,2,3,4, T Kawasaki^1,2,3,4, K Yamana^1,2,3,4, K Suzuki^1,2,3,4, S Jiang^1,2,3,4, H Umezu^1,2,3,4, T Nishiyama^1,2,3,4, K Takahashi^1,2,3,4, T Hamakubo^1,2,3,4, T Kodama^1,2,3,4 and M Naito^1,2,3,4

¹ Division of Urology, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
² Division of Cellular and Molecular Pathology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
³ Perseus Proteomics Inc., Tokyo, Japan
⁴ Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Japan

Correspondence to:
Koichi Wako, MD, Division of Urology, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori 1-757, Chuou-ku, Niigata 951-8510, Japan; kwako{at}med.niigata-u.ac.jp

Aims: The association between the expression of androgen receptor (AR) or androgen-converting enzymes and malignant potential in prostate cancer (PCa) was examined.

Methods: PCa specimens from 44 cases of stage II, 10 cases of stage III, four cases of stage IV and two recurrent cases were semi-quantitatively studied with immunohistochemistry for AR and androgen-converting enzymes.

Results: The expression scores for AR, 5-reductase type 1 (SRD5A1), 5-reductase type 2 (SRD5A2), and aldo-keto reductase family 1 member C3 (AKR1C3) in the metastatic lesion of stage IV or recurrent cancer (n = 6) were 284.2 (30.1), 300 (0.0), 279.2 (51) and 254.2 (74.9), respectively; these scores were significantly higher than the respective scores of 121.8 (82.1), 135.1 (59.7), 167.0 (66.4) and 150.5 (62.8) for stage II and III cancer (n = 54) (p<0.001, p<0.001, p = 0.002 and p = 0.018, respectively). The expression scores for AR and SRD5A1 in stage II and III cancer with Gleason score 7 (n = 19) were 128.7 (72.3) and 150.5 (52.9); these were significantly higher than the scores of 78.8 (67.2) and 100.0 (39.6), respectively, for cancers with a Gleason score of 6 (n = 20) (p = 0.032 and p = 0.002, respectively). The expression scores for AR, SRD5A1 and AKR1C3 in stage II and III cancer with primary Gleason pattern 4 (n = 21) were 158.1 (84.3), 158.3 (61.1) and 173.8 (64.8); these were significantly higher than the scores of 98.6 (72.8), 120.3 (54.7) and 135.6 (57.6), respectively, for cancers with primary Gleason pattern 3 (n = 33) (p = 0.011, p = 0.026 and p = 0.034, respectively). Within Gleason score 9 cancer, the expression scores for AR and SRD5A1 in the primary lesion of stage IV (n = 3) were 276.7 (5.8) and 283.3 (28.9); these scores were significantly higher than the scores of 182.1 (86.0) and 140.0 (56.6), respectively, for stage II and III cancer (n = 7) (p = 0.027 and p = 0.001, respectively).

Conclusions: Both AR and androgen-converting enzymes were upregulated in high-grade or advanced PCa.

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