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Analysis of the prognostic relevance of sex-steroid hormonal receptor mRNA expression in muscle-invasive urothelial carcinoma of the urinary bladder

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Abstract

Muscle-invasive urothelial carcinoma of the urinary bladder (UCB) often recurs following radical cystectomy (RC). An altered expression of sex-steroid hormone receptors has been associated with oncological outcomes of UCB and may represent therapeutic targets. Here the expression of different hormone receptors was measured on mRNA levels in patients treated by RC and associated with outcomes. Androgen receptor (AR), estrogen receptor 1 (ESR1), and progesterone receptor (PGR) mRNA expression was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in RC samples of 87 patients with a median age of 66 (39–88) years. Univariate and multivariate analyses were performed to test associations with pathological and clinical characteristics as well as recurrence-free (RFS) and disease-specific survival (DSS). AR mRNA expression was lower in comparison with ESR1 and PGR expression (p < 0.0001). In univariate analysis, high expression levels of AR were associated with reduced RFS (HR 2.8, p = 0.015) and DSS (HR 2.8, p = 0.010). High AR mRNA expression and a positive lymph node status were independent predictors for reduced RFS (HR 2.5, p = 0.0049) and DSS (HR 3.4, p = 0.009). In patients with low AR mRNA expression, an increased ESR1 and PGR mRNA expression were associated with reduced RFS and DSS. High expression levels of AR are significantly associated with adverse outcome in patients with muscle-invasive UCB following RC. ESR1 and PGR expression status can further stratify patients with low AR expression into subgroups with significantly reduced RFS and DSS. Therapeutic targeting of AR may influence outcomes in patients with UCB.

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References

  1. Carballido EM, Rosenberg JE (2014) Optimal treatment for metastatic bladder cancer. Curr Oncol Rep 16(9):404. https://doi.org/10.1007/s11912-014-0404-2

    Article  CAS  PubMed  Google Scholar 

  2. Dobruch J, Daneshmand S, Fisch M, Lotan Y, Noon AP, Resnick MJ, Shariat SF, Zlotta AR, Boorjian SA (2016) Gender and bladder cancer: a collaborative review of etiology, biology, and outcomes. Eur Urol 69(2):300–310. https://doi.org/10.1016/j.eururo.2015.08.037

    Article  PubMed  Google Scholar 

  3. Burge F, Kockelbergh R (2016) Closing the gender gap: can we improve bladder cancer survival in women? - a systematic review of diagnosis, treatment and outcomes. Urol Int 97:373–379. https://doi.org/10.1159/000449256

    Article  PubMed  Google Scholar 

  4. Lombard AP, Mudryj M (2015) The emerging role of the androgen receptor in bladder cancer. Endocr Relat Cancer 22(5):R265–R277. https://doi.org/10.1530/ERC-15-0209

    Article  CAS  PubMed  Google Scholar 

  5. Mizushima T, Tirador KA, Miyamoto H (2017) Androgen receptor activation: a prospective therapeutic target for bladder cancer? Expert Opin Ther Targets 21(3):249–257. https://doi.org/10.1080/14728222.2017.1280468

    Article  CAS  PubMed  Google Scholar 

  6. Miyamoto H, Yang Z, Chen YT, Ishiguro H, Uemura H, Kubota Y, Nagashima Y, Chang YJ, Hu YC, Tsai MY, Yeh S, Messing EM, Chang C (2007) Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst 99(7):558–568. https://doi.org/10.1093/jnci/djk113

    Article  CAS  PubMed  Google Scholar 

  7. Hsu JW, Hsu I, Xu D, Miyamoto H, Liang L, Wu XR, Shyr CR, Chang C (2013) Decreased tumorigenesis and mortality from bladder cancer in mice lacking urothelial androgen receptor. Am J Pathol 182(5):1811–1820. https://doi.org/10.1016/j.ajpath.2013.01.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Imada S, Akaza H, Ami Y, Koiso K, Ideyama Y, Takenaka T (1997) Promoting effects and mechanisms of action of androgen in bladder carcinogenesis in male rats. Eur Urol 31(3):360–364

    Article  CAS  PubMed  Google Scholar 

  9. Lin C, Yin Y, Stemler K, Humphrey P, Kibel AS, Mysorekar IU, Ma L (2013) Constitutive beta-catenin activation induces male-specific tumorigenesis in the bladder urothelium. Cancer Res 73(19):5914–5925. https://doi.org/10.1158/0008-5472.CAN-12-4198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Birtle AJ, Freeman A, Munson P (2004) The androgen receptor revisited in urothelial carcinoma. Histopathology 45(1):98–99. https://doi.org/10.1111/j.1365-2559.2004.01841.x

    Article  CAS  PubMed  Google Scholar 

  11. Tuygun C, Kankaya D, Imamoglu A, Sertcelik A, Zengin K, Oktay M, Sertcelik N (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 29(1):43–51. https://doi.org/10.1016/j.urolonc.2009.01.033

    Article  CAS  PubMed  Google Scholar 

  12. Boorjian S, Ugras S, Mongan NP, Gudas LJ, You X, Tickoo SK, Scherr DS (2004) Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology 64(2):383–388. https://doi.org/10.1016/j.urology.2004.03.025

    Article  PubMed  Google Scholar 

  13. Miyamoto H, Yao JL, Chaux A, Zheng Y, Hsu I, Izumi K, Chang C, Messing EM, Netto GJ, Yeh S (2012) Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder. BJU Int 109(11):1716–1726. https://doi.org/10.1111/j.1464-410X.2011.10706.x

    Article  CAS  PubMed  Google Scholar 

  14. Zheng Y, Izumi K, Yao JL, Miyamoto H (2011) Dihydrotestosterone upregulates the expression of epidermal growth factor receptor and ERBB2 in androgen receptor-positive bladder cancer cells. Endocr Relat Cancer 18(4):451–464. https://doi.org/10.1530/ERC-11-0010

    Article  CAS  PubMed  Google Scholar 

  15. Mashhadi R, Pourmand G, Kosari F, Mehrsai A, Salem S, Pourmand MR, Alatab S, Khonsari M, Heydari F, Beladi L, Alizadeh F (2014) Role of steroid hormone receptors in formation and progression of bladder carcinoma: a case-control study. Urol J 11(6):1968–1973

    PubMed  Google Scholar 

  16. Mir C, Shariat SF, van der Kwast TH, Ashfaq R, Lotan Y, Evans A, Skeldon S, Hanna S, Vajpeyi R, Kuk C, Alkhateeb S, Morote J, van Rhijn BW, Bostrom P, Yao J, Miyamoto H, Jewett M, Fleshner N, Messing E, Zlotta AR (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(1):24–30. https://doi.org/10.1111/j.1464-410X.2010.09834.x

    Article  PubMed  Google Scholar 

  17. Nam JK, Park SW, Lee SD, Chung MK (2014) Prognostic value of sex-hormone receptor expression in non-muscle-invasive bladder cancer. Yonsei Med J 55(5):1214–1221. https://doi.org/10.3349/ymj.2014.55.5.1214

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bolenz C, Lotan Y, Ashfaq R, Shariat SF (2009) Estrogen and progesterone hormonal receptor expression in urothelial carcinoma of the bladder. Eur Urol 56(6):1093–1095. https://doi.org/10.1016/j.eururo.2009.06.032

    Article  CAS  PubMed  Google Scholar 

  19. Sonpavde G, Okuno N, Weiss H, Yu J, Shen SS, Younes M, Jian W, Lerner SP, Smith CL (2007) Efficacy of selective estrogen receptor modulators in nude mice bearing human transitional cell carcinoma. Urology 69(6):1221–1226. https://doi.org/10.1016/j.urology.2007.02.041

    Article  PubMed  Google Scholar 

  20. Daugherty SE, Lacey JV Jr, Pfeiffer RM, Park Y, Hoover RN, Silverman DT (2013) Reproductive factors and menopausal hormone therapy and bladder cancer risk in the NIH-AARP diet and health study. Int J Cancer 133(2):462–472. https://doi.org/10.1002/ijc.28022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hoffman KL, Lerner SP, Smith CL (2013) Raloxifene inhibits growth of RT4 urothelial carcinoma cells via estrogen receptor-dependent induction of apoptosis and inhibition of proliferation. Hormones Cancer 4(1):24–35. https://doi.org/10.1007/s12672-012-0123-9

    Article  CAS  PubMed  Google Scholar 

  22. Proverbs-Singh T, Feldman JL, Morris MJ, Autio KA, Traina TA (2015) Targeting the androgen receptor in prostate and breast cancer: several new agents in development. Endocr Relat Cancer 22(3):R87–r106. https://doi.org/10.1530/erc-14-0543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Susini T, Bussani C, Marini G, Nori J, Olivieri S, Molino C, Bianchi S, Vezzosi V, Paglierani M, Giachi M, Borrani E, Scarselli G (2010) Preoperative assessment of HER-2/neu status in breast carcinoma: the role of quantitative real-time PCR on core-biopsy specimens. Gynecol Oncol 116(2):234–239. https://doi.org/10.1016/j.ygyno.2009.10.067

    Article  CAS  PubMed  Google Scholar 

  24. Wilson TR, Xiao Y, Spoerke JM, Fridlyand J, Koeppen H, Fuentes E, Huw LY, Abbas I, Gower A, Schleifman EB, Desai R, Fu L, Sumiyoshi T, O'Shaughnessy JA, Hampton GM, Lackner MR (2014) Development of a robust RNA-based classifier to accurately determine ER, PR, and HER2 status in breast cancer clinical samples. Breast Cancer Res Treat 148(2):315–325. https://doi.org/10.1007/s10549-014-3163-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wirtz RM, Sihto H, Isola J, Heikkila P, Kellokumpu-Lehtinen PL, Auvinen P, Turpeenniemi-Hujanen T, Jyrkkio S, Lakis S, Schlombs K, Laible M, Weber S, Eidt S, Sahin U, Joensuu H (2016) Biological subtyping of early breast cancer: a study comparing RT-qPCR with immunohistochemistry. Breast Cancer Res Treat 157(3):437–446. https://doi.org/10.1007/s10549-016-3835-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. von Hardenberg J, Martini T, Knauer A, Strobel P, Becker A, Herrmann E, Schubert C, Steidler A, Bolenz C (2014) Expression and predictive value of lymph-specific markers in urothelial carcinoma of the bladder. Urol Oncol 32(1):54 e59–54.e17. https://doi.org/10.1016/j.urolonc.2013.08.031

    Article  CAS  Google Scholar 

  27. Edge SB BD, Compton CC (2010) Urinary bladder. In: AJCC cancer staging manual. Springer, New York, pp 497–505

  28. Stefanovic S, Wirtz R, Deutsch TM, Hartkopf A, Sinn P, Varga Z, Sobottka B, Sotiris L, Taran FA, Domschke C, Hennigs A, Brucker SY, Sohn C, Schuetz F, Schneeweiss A, Wallwiener M (2017) Tumor biomarker conversion between primary and metastatic breast cancer: mRNA assessment and its concordance with immunohistochemistry. Oncotarget 8(31):51416–51428. https://doi.org/10.18632/oncotarget.18006

    Article  PubMed  PubMed Central  Google Scholar 

  29. Barry WT, Kernagis DN, Dressman HK, Griffis RJ, Hunter JD, Olson JA, Marks JR, Ginsburg GS, Marcom PK, Nevins JR, Geradts J, Datto MB (2010) Intratumor heterogeneity and precision of microarray-based predictors of breast cancer biology and clinical outcome. J Clin Oncol 28(13):2198–2206. https://doi.org/10.1200/jco.2009.26.7245

    Article  PubMed  PubMed Central  Google Scholar 

  30. Laible M, Schlombs K, Kaiser K, Veltrup E, Herlein S, Lakis S, Stohr R, Eidt S, Hartmann A, Wirtz RM, Sahin U (2016) Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer 16:398. https://doi.org/10.1186/s12885-016-2476-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Atmaca A, Al-Batran SE, Wirtz RM, Werner D, Zirlik S, Wiest G, Eschbach C, Claas S, Hartmann A, Ficker JH, Jager E, Brueckl WM (2014) The validation of estrogen receptor 1 mRNA expression as a predictor of outcome in patients with metastatic non-small cell lung cancer. Int J Cancer 134(10):2314–2321. https://doi.org/10.1002/ijc.28571

    Article  CAS  PubMed  Google Scholar 

  32. Sikic D, Breyer J, Hartmann A, Burger M, Erben P, Denzinger S, Eckstein M, Stohr R, Wach S, Wullich B, Keck B, Wirtz RM, Otto W (2017) High androgen receptor mRNA expression is independently associated with prolonged cancer-specific and recurrence-free survival in stage T1 bladder cancer. Transl Oncol 10(3):340–345. https://doi.org/10.1016/j.tranon.2017.01.013

    Article  PubMed  PubMed Central  Google Scholar 

  33. Pentheroudakis G, Kotoula V, Eleftheraki AG, Tsolaki E, Wirtz RM, Kalogeras KT, Batistatou A, Bobos M, Dimopoulos MA, Timotheadou E, Gogas H, Christodoulou C, Papadopoulou K, Efstratiou I, Scopa CD, Papaspyrou I, Vlachodimitropoulos D, Linardou H, Samantas E, Pectasides D, Pavlidis N, Fountzilas G (2013) Prognostic significance of ESR1 gene amplification, mRNA/protein expression and functional profiles in high-risk early breast cancer: a translational study of the Hellenic cooperative oncology group (HeCOG). PLoS One 8(7):e70634. https://doi.org/10.1371/journal.pone.0070634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tramm T, Sorensen BS, Overgaard J, Alsner J (2013) Optimal reference genes for normalization of qRT-PCR data from archival formalin-fixed, paraffin-embedded breast tumors controlling for tumor cell content and decay of mRNA. Diagn Mol Pathol 22(3):181–187. https://doi.org/10.1097/PDM.0b013e318285651e

    Article  CAS  PubMed  Google Scholar 

  35. Rinaldetti S, Wirtz RM, Worst TS, Eckstein M, Weiss CA, Breyer J, Otto W, Bolenz C, Hartmann A, Erben P (2017) FOXM1 predicts overall and disease specific survival in muscle-invasive urothelial carcinoma and presents a differential expression between bladder cancer subtypes. Oncotarget 8:47595–47606. https://doi.org/10.18632/oncotarget.17394

    Article  PubMed  PubMed Central  Google Scholar 

  36. Breyer J, Wirtz RM, Otto W, Erben P, Kriegmair MC, Stoehr R, Eckstein M, Eidt S, Denzinger S, Burger M, Hartmann A (2017) In stage pT1 non-muscle-invasive bladder cancer (NMIBC), high KRT20 and low KRT5 mRNA expression identify the luminal subtype and predict recurrence and survival. Virchows Arch 470(3):267–274. https://doi.org/10.1007/s00428-017-2064-8

    Article  CAS  PubMed  Google Scholar 

  37. Kauffman EC, Robinson BD, Downes MJ, Powell LG, Lee MM, Scherr DS, Gudas LJ, Mongan NP (2011) Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer. Mol Carcinog 50(12):931–944. https://doi.org/10.1002/mc.20758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Otto W, Denzinger S, Fritsche HM, Burger M, Rossler W, Bertz S, May M, Hartmann A, Hofstadter F, Wieland WF, Eder F (2013) Introduction and first clinical application of a simplified immunohistochemical validation system confirms prognostic impact of KI-67 and CK20 for stage T1 urothelial bladder carcinoma: single-center analysis of eight biomarkers in a series of three hundred six patients. Clin Genitourin Cancer 11(4):537–544. https://doi.org/10.1016/j.clgc.2013.05.001

    Article  PubMed  Google Scholar 

  39. Hartmann A, Bertz S, Keck B, Dyrskjot L, Orntoft T, Wullich B, Hake R, Eidt S, Wirtz R (2012) Abstract 3654: prognostic role of androgen receptor in bladder cancer. In: Proceedings: AACR 103rd Annual Meeting. https://doi.org/10.1158/1538-7445.AM2012-3654

  40. Rabiau N, Dechelotte P, Adjakly M, Kemeny JL, Guy L, Boiteux JP, Kwiatkowski F, Bignon YJ, Bernard-Gallon D (2011) BRCA1, BRCA2, AR and IGF-I expression in prostate cancer: correlation between RT-qPCR and immunohistochemical detection. Oncol Rep 26(3):695–702. https://doi.org/10.3892/or.2011.1339

    Article  CAS  PubMed  Google Scholar 

  41. Breyer J, Otto W, Wirtz RM, Wullich B, Keck B, Erben P, Kriegmair MC, Stoehr R, Eckstein M, Laible M, Schlombs K, Eidt S, Denzinger S, Burger M, Hartmann A, Consortium B (2016) ERBB2 expression as potential risk-stratification for early cystectomy in patients with pT1 bladder cancer and concomitant carcinoma in situ. Urol Int 98:282–289. https://doi.org/10.1159/000453670

    Article  CAS  PubMed  Google Scholar 

  42. Network CGAR (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507(7492):315–322. https://doi.org/10.1038/nature12965

    Article  CAS  Google Scholar 

  43. Shen SS, Smith CL, Hsieh JT, Yu J, Kim IY, Jian W, Sonpavde G, Ayala GE, Younes M, Lerner SP (2006) Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer 106(12):2610–2616. https://doi.org/10.1002/cncr.21945

    Article  CAS  PubMed  Google Scholar 

  44. Schweizer MT, Yu EY (2017) AR-signaling in human malignancies: prostate cancer and beyond. Cancers 9(1). https://doi.org/10.3390/cancers9010007

  45. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121(7):2750–2767. https://doi.org/10.1172/jci45014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Robinson JL, Macarthur S, Ross-Innes CS, Tilley WD, Neal DE, Mills IG, Carroll JS (2011) Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1. EMBO J 30(15):3019–3027. https://doi.org/10.1038/emboj.2011.216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Izumi K, Taguri M, Miyamoto H, Hara Y, Kishida T, Chiba K, Murai T, Hirai K, Suzuki K, Fujinami K, Ueki T, Udagawa K, Kitami K, Moriyama M, Miyoshi Y, Tsuchiya F, Ikeda I, Kobayashi K, Sato M, Morita S, Noguchi K, Uemura H (2014) Androgen deprivation therapy prevents bladder cancer recurrence. Oncotarget 5(24):12665–12674

    Article  PubMed  PubMed Central  Google Scholar 

  48. Shiota M, Kiyoshima K, Yokomizo A, Takeuchi A, Kashiwagi E, Dejima T, Takahashi R, Inokuchi J, Tatsugami K, Eto M (2017) Suppressed recurrent bladder cancer after androgen suppression with androgen deprivation therapy or 5alpha-reductase inhibitor. J Urol 197(2):308–313. https://doi.org/10.1016/j.juro.2016.08.006

    Article  CAS  PubMed  Google Scholar 

  49. Takeuchi H, Mmeje CO, Jinesh GG, Taoka R, Kamat AM (2015) Sequential gemcitabine and tamoxifen treatment enhances apoptosis and blocks transformation in bladder cancer cells. Oncol Rep 34(5):2738–2744. https://doi.org/10.3892/or.2015.4220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hsu CH, Chen J, Wu CY, Cheng AL, Pu YS (2001) Combination chemotherapy of cisplatin, methotrexate, vinblastine, and high-dose tamoxifen for transitional cell carcinoma. Anticancer Res 21(1B):711–715

    CAS  PubMed  Google Scholar 

  51. Choi W, Porten S, Kim S, Willis D, Plimack ER, Hoffman-Censits J, Roth B, Cheng T, Tran M, Lee IL, Melquist J, Bondaruk J, Majewski T, Zhang S, Pretzsch S, Baggerly K, Siefker-Radtke A, Czerniak B, Dinney CP, McConkey DJ (2014) Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25(2):152–165. https://doi.org/10.1016/j.ccr.2014.01.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Damrauer JS, Hoadley KA, Chism DD, Fan C, Tiganelli CJ, Wobker SE, Yeh JJ, Milowsky MI, Iyer G, Parker JS, Kim WY (2014) Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A 111(8):3110–3115. https://doi.org/10.1073/pnas.1318376111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Rinaldetti S, Worst T, Steidler A, Weis C-A, Hartmann A, Bolenz C, Erben P (2016) Subclassification and outcome prediction of patients with muscle invasive urothelial carcinoma (MIUC) treated by radical cystectomy (RC) with a NanoString based molecular screening. J Clin Oncol 34, Chicago (suppl; abstr 4525)

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Acknowledgments

The authors thank Annette Steidler, Stefanie Herlein, and Silke Claas for excellent technical support.

Philipp Erben, Danijel Sikic, Ralph M. Wirtz, Thomas Martini, Johannes Breyer, Wolfgang Otto, Bastian Keck, Arndt Hartmann, and Christian Bolenz are members of the BRIDGE Consortium e.V.

Funding

This study was funded in parts by the German Cancer Aid (Deutsche Krebshilfe (DKH)), grant number 110541.

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Author notes

  1. Philipp Erben and Danijel Sikic contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

    Philipp Erben

  2. Department of Urology and Pediatric Urology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany

    Danijel Sikic & Bastian Keck

  3. Stratifyer Molecular Pathology GmbH, Cologne, Germany

    Ralph M. Wirtz

  4. Department of Urology and Pediatric Urology, University of Ulm, Ulm, Germany

    Thomas Martini & Christian Bolenz

  5. Institute of Pathology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

    Cleo-Aron Weis

  6. Department of Urology, University of Regensburg, Regensburg, Germany

    Johannes Breyer & Wolfgang Otto

  7. Institute of Pathology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany

    Arndt Hartmann

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on behalf of the BRIDGE Consortium e.V.

  • Philipp Erben
  • , Danijel Sikic
  • , Ralph M. Wirtz
  • , Thomas Martini
  • , Johannes Breyer
  • , Wolfgang Otto
  • , Bastian Keck
  • , Arndt Hartmann
  •  & Christian Bolenz

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Correspondence to Danijel Sikic.

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Informed consent was obtained from all the individual participants included in the study. The study was conducted after approval of the local ethics committee (board (Number 2013-517 N-MA/ 2016-814R-MA).

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Ralph M. Wirtz is a founder of STRATIFYER Molecular Pathology GmbH. All other authors declare that they have no conflict of interest.

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Erben, P., Sikic, D., Wirtz, R.M. et al. Analysis of the prognostic relevance of sex-steroid hormonal receptor mRNA expression in muscle-invasive urothelial carcinoma of the urinary bladder. Virchows Arch 474, 209–217 (2019). https://doi.org/10.1007/s00428-018-2496-9

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