High testosterone levels in prostate tissue obtained by needle biopsy correlate with poor-prognosis factors in prostate cancer patients

BMC Cancer

Yoshinobu Kubota^1,11  Masaoki Harada⁶  Seijiro Honma³  Hideki Sakai²  Norio Nonomura⁷  Yoshiki Sugimura¹  Atsushi Mizokami⁹  Tomohiko Ichikawa⁸  Naoya Masumori^1,10  Yasuhiro Shibata⁴  Kazuhiro Suzuki⁴  Satoshi Morita⁵  Kentaro Sakamaki⁵  Susumu Umemoto^1,11  Hiroji Uemura^1,11  Yasuhide Miyoshi^1,11 

[1]Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Japan

[2]Department of Nephro-urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

[3]ASKA Pharma Medical Co., Ltd, Kawasaki, Japan

[4]Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan

[5]Department of Biostatistics and Epidemiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan

[6]Department of Urology and Pathology, Kanagawa Cancer Center, Asahi-ku, Yokohama, Japan

[7]Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan

[8]Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan

[9]Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

[10]Department of Urologic Surgery and Andrology, Sapporo Medical University School of Medicine, Sapporo, Japan

[11]Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

关键词: Dihydrotestosterone;    Testosterone;    Androgen;    Prostate cancer;   

Others  :  1121023
DOI  :  10.1186/1471-2407-14-717

 received in 2014-05-31, accepted in 2014-09-24,  发布年份 2014

【 摘 要 】

Background

There is currently no consensus on the correlations between androgen concentrations in prostate tissue and blood and stage and pathological grade of prostate cancer. In this study, we used a newly-developed ultra-sensitive liquid-chromatography tandem mass spectrometry method to measure testosterone (T) and dihydrotestosterone (DHT) concentrations in blood and needle biopsy prostate specimens from patients with prostate cancer.

Methods

We analyzed androgen levels in 196 men diagnosed with prostate cancer. All patients had undergone systematic needle biopsy, and an additional needle biopsy from the peripheral zone was conducted for the simultaneous determination of T and DHT. We analyzed the relationships between T and DHT levels in tissue and blood and Gleason score, clinical stage, and percentage of positive biopsy cores, using multivariate analysis.

Results

The median T and DHT levels in blood were 3551.0 pg/mL and 330.5 pg/mL, respectively. There was a strong correlation between serum T and DHT. The median T and DHT levels in prostate tissue were 0.5667 pg/mg and 7.0625 pg/mg, respectively. In multivariate analysis, serum prostate-specific antigen and tissue T levels were significantly associated with poor prognosis; high T levels in prostate tissue were significantly related to high Gleason score (p = 0.041), advanced clinical stage (p = 0.002), and a high percentage of positive biopsy cores (p = 0.001).

Conclusions

The results of this study indicate that high T levels in prostate tissue are related to high Gleason score, advanced clinical stage, and a high percentage of positive biopsy cores in patients with prostate cancer. T level in needle biopsy specimens may therefore be a useful prognostic factor in prostate cancer patients.

【 授权许可】

   
2014 Miyoshi et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Belanger B, Belanger A, Labrie F, Dupont A, Cusan L, Monfette G: Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men. J Steroid Biochem 1989, 32(5):695-698.
• [2]Mohler JL, Gregory CW, Ford OH 3rd, Kim D, Weaver CM, Petrusz P, Wilson EM, French FS: The androgen axis in recurrent prostate cancer. Clin Cancer Res 2004, 10(2):440-448.
• [3]Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD, Nelson PS: Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008, 68(11):4447-4454.
• [4]Titus MA, Schell MJ, Lih FB, Tomer KB, Mohler JL: Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin Cancer Res 2005, 11(13):4653-4657.
• [5]Yamashita K, Miyashiro Y, Maekubo H, Okuyama M, Honma S, Takahashi M, Numazawa M: Development of highly sensitive quantification method for testosterone and dihydrotestosterone in human serum and prostate tissue by liquid chromatography-electrospray ionization tandem mass spectrometry. Steroids 2009, 74(12):920-926.
• [6]Mizokami A, Koh E, Fujita H, Maeda Y, Egawa M, Koshida K, Honma S, Keller ET, Namiki M: The adrenal androgen androstenediol is present in prostate cancer tissue after androgen deprivation therapy and activates mutated androgen receptor. Cancer Res 2004, 64(2):765-771.
• [7]Matsui F, Koh E, Yamamoto K, Sugimoto K, Sin HS, Maeda Y, Honma S, Namiki M: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of salivary testosterone and cortisol in healthy men for utilization in the diagnosis of late-onset hypogonadism in males. Endocr J 2009, 56(9):1083-1093.
• [8]Ghanadian R, Puah CM: Relationships between oestradiol-17 beta, testosterone, dihydrotestosterone and 5 alpha-androstane-3 alpha, 27 beta-diol in human benign hypertrophy and carcinoma of the prostate. J Endocrinol 1981, 88(2):255-262.
• [9]Nishiyama T, Ikarashi T, Hashimoto Y, Suzuki K, Takahashi K: Association between the dihydrotestosterone level in the prostate and prostate cancer aggressiveness using the Gleason score. J Urol 2006, 176(4 Pt 1):1387-1391.
• [10]Nishiyama T, Ikarashi T, Hashimoto Y, Wako K, Takahashi K: The change in the dihydrotestosterone level in the prostate before and after androgen deprivation therapy in connection with prostate cancer aggressiveness using the Gleason score. J Urol 2007, 178(4 Pt 1):1282-1288. discussion 1288–1289
• [11]Shibata Y, Suzuki K, Arai S, Miyoshi Y, Umemoto S, Masumori N, Kamiya N, Ichikawa T, Kitagawa Y, Mizokami A, Sugimura Y, Nonomura N, Sakai H, Honma S, Kubota Y: Impact of pre-treatment prostate tissue androgen content on the prediction of castration-resistant prostate cancer development in patients treated with primary androgen deprivation therapy. Androl 2013, 1(3):505-511.
• [12]Vermeulen A, Giagulli VA, De Schepper P, Buntinx A, Stoner E: Hormonal effects of an orally active 4-azasteroid inhibitor of 5 alpha-reductase in humans. Prostate 1989, 14(1):45-53.
• [13]Geller J, Albert J, Lopez D, Geller S, Niwayama G: Comparison of androgen metabolites in benign prostatic hypertrophy (BPH) and normal prostate. J Clin Endocrinol Metab 1976, 43(3):686-688.
• [14]Gustafsson O, Norming U, Gustafsson S, Eneroth P, Astrom G, Nyman CR: Dihydrotestosterone and testosterone levels in men screened for prostate cancer: a study of a randomized population. Br J Urol 1996, 77(3):433-440.
• [15]Walsh PC, Hutchins GM, Ewing LL: Tissue content of dihydrotestosterone in human prostatic hyperplasis is not supranormal. J Clin Invest 1983, 72(5):1772-1777.
• [16]Thomas LN, Douglas RC, Lazier CB, Gupta R, Norman RW, Murphy PR, Rittmaster RS, Too CK: Levels of 5alpha-reductase type 1 and type 2 are increased in localized high grade compared to low grade prostate cancer. J Urol 2008, 179(1):147-151.
• [17]de Winter JA, Trapman J, Brinkmann AO, Boersma WJ, Mulder E, Schroeder FH, Claassen E, van der Kwast TH: Androgen receptor heterogeneity in human prostatic carcinomas visualized by immunohistochemistry. J Pathol 1990, 160(4):329-332.
• [18]Garcia-Cruz E, Piqueras M, Huguet J, Peri L, Izquierdo L, Musquera M, Franco A, Alvarez-Vijande R, Ribal MJ, Alcaraz A: Low testosterone levels are related to poor prognosis factors in men with prostate cancer prior to treatment. BJU Int 2012, 110(11 Pt B):E541-E546.
• [19]Morgentaler A: Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol 2006, 50(5):935-939.