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

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, 5alpha-reductase type 1 (SRD5A1), 5alpha-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 < or =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 > or =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 < or =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.

• Authors: K Wako, T Kawasaki, K Yamana, K Suzuki, S Jiang, H Umezu, T Nishiyama, K Takahashi, T Hamakubo, T Kodama, M Naito
• Journal: Journal of clinical pathology (J Clin Pathol) Vol. 61 Issue 4 Pg. 448-54 (Apr 2008) ISSN: 1472-4146 [Electronic] England
• PMID: 17720776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AR protein, human
• Biomarkers, Tumor
• Neoplasm Proteins
• Receptors, Androgen
• 3-Hydroxysteroid Dehydrogenases
• Hydroxyprostaglandin Dehydrogenases
• AKR1C3 protein, human
• Aldo-Keto Reductase Family 1 Member C3
• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Topics

• 3-Hydroxysteroid Dehydrogenases (metabolism)
• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase (metabolism)
• Adult
• Aged
• Aldo-Keto Reductase Family 1 Member C3
• Biomarkers, Tumor (metabolism)
• Humans
• Hydroxyprostaglandin Dehydrogenases (metabolism)
• Immunoenzyme Techniques
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Proteins (metabolism)
• Neoplasm Staging
• Prostatectomy
• Prostatic Neoplasms (metabolism, pathology, surgery)
• Receptors, Androgen (metabolism)
• Tumor Cells, Cultured