Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer
- K Wako1,2,3,4,
- T Kawasaki1,2,3,4,
- K Yamana1,2,3,4,
- K Suzuki1,2,3,4,
- S Jiang1,2,3,4,
- H Umezu1,2,3,4,
- T Nishiyama1,2,3,4,
- K Takahashi1,2,3,4,
- T Hamakubo1,2,3,4,
- T Kodama1,2,3,4,
- M Naito1,2,3,4
- 1Division of Urology, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- 2Division of Cellular and Molecular Pathology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- 3Perseus Proteomics Inc., Tokyo, Japan
- 4Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Japan
- 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
- Accepted 6 August 2007
- Published Online First 24 August 2007
Abstract
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, 5α-reductase type 1 (SRD5A1), 5α-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.
Footnotes
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Funding: This study was partly supported by the Program of Fundamental Studies in Health Sciences of the National Institute of Biochemical Innovation (NIBIO), by the Focus 21 project of the New Energy and Industrial Technology Development Organization (NEDO), and by the Special Coordination Fund for Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology.
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Competing interests: None.
