The Expression of Androgen Receptor and Its Variants in Human Prostate Cancer Tissue According to Disease Status, and Its Prognostic Significance

Overview

Journal World J Mens Health

Date 2018 May 15

PMID 29756415

Citations 2

Authors

Sung Woo Park

Jung Hee Kim

Hyun Jung Lee

Dong Hoon Shin

Sang Don Lee

Sik Yoon

Affiliations

Soon will be listed here.

Abstract

Purpose: To evaluate changes in the expression of androgen receptor (AR) and its variants (ARVs) in human prostate cancer (PCa) tissues according to disease status, and its prognostic significance following radical prostatectomy (RP).

Materials And Methods: A total of 282 PCa cases were evaluated, which included 252 localized PCa, 8 metastatic castration resistant prostate cancer (CRPC), and 22 benign prostatic hyperplasia (BPH) cases. Samples were collected from patients who underwent RP or transurethral resection and were stored in ethically approved tissue banks. Quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were performed for AR and ARVs. Each tissue was confirmed as cancerous (greater than 80%) using hematoxylin and eosin staining. AR and ARVs expression was compared according to disease status. The biochemical recurrence free survival (BCRFS) rates in men with localized PCa was analyzed according to AR and ARV7 expression using the Kaplan-Meier curve.

Results: Only 58 of the 252 localized PCa were included in the analysis because of insufficient cancer tissue. AR and ARV7 mRNA expression was higher in the CRPC tissue than in the localized PCa tissue (p=0.025, p=0.002, respectively). In localized PCa tissue, high AR mRNA and protein level was associated with a low BCRFS rate (log-ranked, p=0.019, p<0.001, respectively).

Conclusions: Overall AR and ARV7 mRNA expression levels were increased in CRPC tissues compared to localized PCa and BPH tissues. High AR protein and mRNA expression in the tumor tissue may be considered a predictive factor of BCRFS following RP.

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References

Sweat S, Pacelli A, Bergstralh E, Slezak J, Cheng L, Bostwick D . Androgen receptor expression in prostate cancer lymph node metastases is predictive of outcome after surgery. J Urol. 1999; 161(4):1233-7. View

Henshall S, Quinn D, Lee C, Head D, Golovsky D, Brenner P . Altered expression of androgen receptor in the malignant epithelium and adjacent stroma is associated with early relapse in prostate cancer. Cancer Res. 2001; 61(2):423-7. View

Segawa N, Mori I, Utsunomiya H, Nakamura M, Nakamura Y, Shan L . Prognostic significance of neuroendocrine differentiation, proliferation activity and androgen receptor expression in prostate cancer. Pathol Int. 2001; 51(6):452-9. DOI: 10.1046/j.1440-1827.2001.01226.x. View

Li R, Wheeler T, Dai H, Frolov A, Thompson T, Ayala G . High level of androgen receptor is associated with aggressive clinicopathologic features and decreased biochemical recurrence-free survival in prostate: cancer patients treated with radical prostatectomy. Am J Surg Pathol. 2004; 28(7):928-34. DOI: 10.1097/00000478-200407000-00013. View

Ricciardelli C, Choong C, Buchanan G, Vivekanandan S, Neufing P, Stahl J . Androgen receptor levels in prostate cancer epithelial and peritumoral stromal cells identify non-organ confined disease. Prostate. 2004; 63(1):19-28. DOI: 10.1002/pros.20154. View

Culig Z, Bartsch G . Androgen axis in prostate cancer. J Cell Biochem. 2006; 99(2):373-81. DOI: 10.1002/jcb.20898. View

Litvinov I, Antony L, Dalrymple S, Becker R, Cheng L, Isaacs J . PC3, but not DU145, human prostate cancer cells retain the coregulators required for tumor suppressor ability of androgen receptor. Prostate. 2006; 66(12):1329-38. DOI: 10.1002/pros.20483. View

Guo Z, Dai B, Jiang T, Xu K, Xie Y, Kim O . Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell. 2006; 10(4):309-19. DOI: 10.1016/j.ccr.2006.08.021. View

Rosner I, Ravindranath L, Furusato B, Chen Y, Gao C, Cullen J . Higher tumor to benign ratio of the androgen receptor mRNA expression associates with prostate cancer progression after radical prostatectomy. Urology. 2007; 70(6):1225-9. DOI: 10.1016/j.urology.2007.09.010. View

10.

Hu R, Dunn T, Wei S, Isharwal S, Veltri R, Humphreys E . Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res. 2009; 69(1):16-22. PMC: 2614301. DOI: 10.1158/0008-5472.CAN-08-2764. View

11.

Wikstrom P, Marusic J, Stattin P, Bergh A . Low stroma androgen receptor level in normal and tumor prostate tissue is related to poor outcome in prostate cancer patients. Prostate. 2009; 69(8):799-809. DOI: 10.1002/pros.20927. View

12.

Guo Z, Yang X, Sun F, Jiang R, Linn D, Chen H . A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res. 2009; 69(6):2305-13. PMC: 2672822. DOI: 10.1158/0008-5472.CAN-08-3795. View

13.

Ishikura N, Kawata H, Nishimoto A, Nakamura R, Ishii N, Aoki Y . Establishment and characterization of an androgen receptor-dependent, androgen-independent human prostate cancer cell line, LNCaP-CS10. Prostate. 2009; 70(5):457-66. DOI: 10.1002/pros.21079. View

14.

Sun S, Sprenger C, Vessella R, Haugk K, Soriano K, Mostaghel E . Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J Clin Invest. 2010; 120(8):2715-30. PMC: 2912187. DOI: 10.1172/JCI41824. View

15.

Molina A, Belldegrun A . Novel therapeutic strategies for castration resistant prostate cancer: inhibition of persistent androgen production and androgen receptor mediated signaling. J Urol. 2011; 185(3):787-94. DOI: 10.1016/j.juro.2010.10.042. View

16.

Minner S, Enodien M, Sirma H, Luebke A, Krohn A, Mayer P . ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of antihormonal therapy. Clin Cancer Res. 2011; 17(18):5878-88. DOI: 10.1158/1078-0432.CCR-11-1251. View

17.

Zhao H, Coram M, Nolley R, Reese S, Young S, Peehl D . Transcript levels of androgen receptor variant AR-V1 or AR-V7 do not predict recurrence in patients with prostate cancer at indeterminate risk for progression. J Urol. 2012; 188(6):2158-64. DOI: 10.1016/j.juro.2012.08.014. View

18.

Guerrero J, Alfaro I, Gomez F, Protter A, Bernales S . Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer. Prostate. 2013; 73(12):1291-305. DOI: 10.1002/pros.22674. View

19.

Peer A, Gottfried M, Sinibaldi V, Carducci M, Eisenberger M, Sella A . Comparison of abiraterone acetate versus ketoconazole in patients with metastatic castration resistant prostate cancer refractory to docetaxel. Prostate. 2013; 74(4):433-40. PMC: 4696030. DOI: 10.1002/pros.22765. View

20.

Antonarakis E, Lu C, Wang H, Luber B, Nakazawa M, Roeser J . AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014; 371(11):1028-38. PMC: 4201502. DOI: 10.1056/NEJMoa1315815. View