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Androgen receptor expression is associated with adverse pathological features in ureteral but not in pelvicalyceal urothelial carcinomas of the upper urinary tract

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Abstract

Purpose

This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC).

Methods

AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS).

Results

Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system (p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS.

Conclusions

In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors.

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Abbreviations

AR:

Androgen receptor

CIS:

Carcinoma in situ

CSS:

Cancer-specific survival

HG:

High grade

OS:

Overall survival

LG:

Low grade

LVI:

Lymphovascular invasion

RFS:

Recurrence-free survival

RNU:

Radical nephroureterectomy

UTUC:

Upper urinary tract urothelial carcinoma

References

  1. Hartge P, Harvey EB, Linehan WM et al (1990) Unexplained excess risk of bladder cancer in men. J Natl Cancer Inst 82:1636–1640

    Article  CAS  PubMed  Google Scholar 

  2. Gakis G, Stenzl A (2013) Gender-specific differences in muscle-invasive bladder cancer: the concept of sex steroid sensitivity. World J Urol 31:1059–1064. doi:10.1007/s00345-013-1037-z

    Article  CAS  PubMed  Google Scholar 

  3. Dobruch J, Daneshmand S, Fisch M et al (2016) Gender and bladder cancer: a collaborative review of etiology, biology, and outcomes. Eur Urol 69:300–310. doi:10.1016/j.eururo.2015.08.037

    Article  PubMed  Google Scholar 

  4. Lucca I, Fajkovic H, Klatte T (2014) Sex steroids and gender differences in nonmuscle invasive bladder cancer. Curr Opin Urol 24:500–505. doi:10.1097/MOU.0000000000000092

    Article  PubMed  Google Scholar 

  5. Lombard AP, Mudryj M (2015) The emerging role of the androgen receptor in bladder cancer. Endocr Relat Cancer 22:265–277. doi:10.1530/ERC-15-0209

    Article  Google Scholar 

  6. Boorjian S, Ugras S, Mongan NP et al (2004) Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology 64:383–388. doi:10.1016/j.urology.2004.03.025

    Article  PubMed  Google Scholar 

  7. Tuygun C, Kankaya D, Imamoglu A et al (2011) Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression. Urol Oncol Semin Orig Investig 29:43–51. doi:10.1016/j.urolonc.2009.01.033

    Article  CAS  Google Scholar 

  8. Mir C, Shariat SF, Van Der Kwast TH et al (2011) Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study. BJU Int 108:24–30. doi:10.1111/j.1464-410X.2010.09834.x

    Article  PubMed  Google Scholar 

  9. Williams EM, Higgins JP, Sangoi AR et al (2015) Androgen receptor immunohistochemistry in genitourinary neoplasms. Int Urol Nephrol 47:81–85. doi:10.1007/s11255-014-0834-7

    Article  CAS  PubMed  Google Scholar 

  10. Shyr CR, Chen CC, Hsieh TF et al (2013) The expression and actions of androgen receptor in upper urinary tract urothelial carcinoma (UUTUC) tissues and the primary cultured cells. Endocrine 43:191–199. doi:10.1007/s12020-012-9762-4

    Article  CAS  PubMed  Google Scholar 

  11. Rau K, Chen Y, Sun M, Kang H (2011) Prognostic effects and regulation of activin A, maspin, and the androgen receptor in upper urinary tract urothelial carcinoma. Anticancer Res 31:1713–1720

    CAS  PubMed  Google Scholar 

  12. Green DA, Rink M, Xylinas E et al (2013) Urothelial carcinoma of the bladder and the upper tract: disparate twins. J Urol 189:1214–1221. doi:10.1016/j.juro.2012.05.079

    Article  PubMed  Google Scholar 

  13. Rink M, Ehdaie B, Cha EK et al (2012) Stage-specific impact of tumor location on oncologic outcomes in patients with upper and lower tract urothelial carcinoma following radical surgery. Eur Urol 62:677–684. doi:10.1016/j.eururo.2012.02.018

    Article  PubMed  Google Scholar 

  14. Margulis V, Shariat SF, Matin SF et al (2009) Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer 115:1224–1233. doi:10.1002/cncr.24135

    Article  PubMed  Google Scholar 

  15. Krabbe L-M, Bagrodia A, Haddad AQ et al (2015) Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper urinary tract. J Urol 193:1486–1493. doi:10.1016/j.juro.2014.11.007

    Article  CAS  PubMed  Google Scholar 

  16. Rink M, Fajkovic H, Cha EK et al (2012) Death certificates are valid for the determination of cause of death in patients with upper and lower tract urothelial carcinoma. Eur Urol 61:854–855. doi:10.1016/j.eururo.2011.12.055

    Article  PubMed  Google Scholar 

  17. Edge S, Byrd DR, Compton CC et al (2010) AJCC cancer staging manual, 7th edn. Springer, New York

    Google Scholar 

  18. Epstein JI, Amin MB, Reuter VR, Mostofi FK (1998) The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol 22:1435–1448

    Article  CAS  PubMed  Google Scholar 

  19. Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140

    CAS  PubMed  Google Scholar 

  20. Lai M-N, Wang S-M, Chen P-C et al (2010) Population-based case-control study of Chinese herbal products containing aristolochic acid and urinary tract cancer risk. J Natl Cancer Inst 102:179–186. doi:10.1093/jnci/djp467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chen C-H, Dickman KG, Moriya M et al (2012) Aristolochic acid-associated urothelial cancer in Taiwan. Proc Natl Acad Sci USA 109:8241–8246. doi:10.1073/pnas.1119920109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hsieh S-C, Lin I-H, Tseng W-L et al (2008) Prescription profile of potentially aristolochic acid containing Chinese herbal products: an analysis of National Health Insurance data in Taiwan between 1997 and 2003. Chin Med 3:13. doi:10.1186/1749-8546-3-13

    Article  PubMed  PubMed Central  Google Scholar 

  23. Krabbe LM, Bagrodia A, Westerman ME et al (2016) Molecular profile of urothelial carcinoma of the upper urinary tract: Are pelvicalyceal and ureteral tumors different? World J Urol 34:105–112. doi:10.1007/s00345-015-1584-6

    Article  CAS  PubMed  Google Scholar 

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Authors contribution

Margulis V, Lotan Y and Shariat SF were involved in protocol/project development. Haitel A, Karam JA, Wood CG, Rouprêt M, Margulis V, Karakiewicz PI, Briganti A, Raman JD, Rioux-Leclercq N, Bensalah K, Lotan Y, Remzi M, Robinson BD and Shariat SF were involved in data collection or management. Wirth G, Soria F and Moschini M were involved in data analysis. Wirth G and Shariat SF wrote the manuscript. Wirth G, Soria F, Moschini M, Haitel A, Klatte T, Hassler M, Karam JA, Wood CG, Rouprêt M, Margulis V, Briganti A, Raman JD, Bensalah K, Rioux-Leclercq N, Robinson BD, Lotan Y, Remzi M and Shariat SF edited the manuscript.

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Correspondence to S. F. Shariat.

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The authors declare that there is no conflict of interest or financial disclosures to be reported regarding this work.

Ethical standard

This was an institutional review board-approved study, with all participating sites providing the necessary institutional data use agreements before initiation of the study.

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Wirth, G.J., Haitel, A., Moschini, M. et al. Androgen receptor expression is associated with adverse pathological features in ureteral but not in pelvicalyceal urothelial carcinomas of the upper urinary tract. World J Urol 35, 943–949 (2017). https://doi.org/10.1007/s00345-016-1946-8

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  • DOI: https://doi.org/10.1007/s00345-016-1946-8

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