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WHO 1973 grade 3 and infiltrative growth pattern proved, aberrant E-cadherin expression tends to be of predictive value for progression in a series of stage T1 high-grade bladder cancer after organ-sparing approach

  • Urology - Original Paper
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Abstract

Purpose

Stage pT1 urothelial bladder cancer (UBC) is characterized as a challenging subentity of urothelial carcinoma with an unforeseeable clinical course. In addition to more or less established clinical and histopathological features, we evaluated the role of epithelial–mesenchymal transition (EMT) marker E-cadherin, shown to be of prognostic value in muscle-invasive disease, regarding the prognosis of stage pT1 high-grade (hg) UBC.

Methods

Tissue of 226 stage pT1 hg UBC patients from transurethral resection could be immunostained for E-cadherin. Kaplan–Meier analysis and univariate and multivariate Cox regression analyses regarding progression-free (PFS) and cancer-specific survival (CSS) were performed.

Results

Aberrant expression of E-cadherin was recognized in 74% of patients. Kaplan–Meier analysis showed that aberrant E-cadherin expression was associated with worse 10-year PFS (62 vs. 90%, p = 0.045). In univariate analysis, aberrant E-cadherin staining, associated carcinoma in situ, grading 3 after WHO classification 1973 and infiltrative growth pattern at the invasion front were the statistically significant predictive factors for worse PFS, only infiltrative growth pattern for CSS. With regard to progression, grading 3 after WHO classification of 1973 (HR 6.49; CI 1.54–27.28, p = 0.011) and infiltrative tumor invasion pattern (HR 2.06; CI 1.10–3.86, p = 0.024) revealed as independent factors for PFS, and there was a trend also for E-cadherin expression (HR 0.45; CI 0.19–1.06; p = 0.068). Regarding CSS, infiltrative tumor growth pattern (HR 3.79; CI 1.67–8.60, p = 0.001) was the only statistically significantly independent predictive factor in multivariate Cox regression analysis.

Conclusions

Beside invasion growth pattern and WHO grading 1973 that achieved to be independent prognostic factors, there was a trend for the parameter E-cadherin expression to be of predictive value for PFS in stage pT1 hg urothelial bladder carcinoma after organ-sparing approach. Further studies on genetic level are warranted to define the distinct role of EMT in early-invasive UBC.

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References

  1. Baum B, Settleman J, Quinlan MP (2008) Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol 19:294–308

    Article  CAS  PubMed  Google Scholar 

  2. Shook D, Keller R (2003) Mechanisms, mechanics and function of epithelial–mesenchymal transitions in early development. Mech Dev 120:1351–1383

    Article  CAS  PubMed  Google Scholar 

  3. Tarin D (2005) The fallacy of epithelial mesenchymal transition in neoplasia. Cancer Res 65:5996–6001

    Article  CAS  PubMed  Google Scholar 

  4. McConkey DJ, Lee S, Choi W et al (2010) Molecular genetics of bladder cancer: emerging mechanisms of tumour initiation and progression. Urol Oncol Semin Invest 28:429–440

    Article  CAS  Google Scholar 

  5. Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T (2005) Opinion: migrating cancer stem cells—an integrated concept of malignant tumour progression. Nat Rev Cancer 5(9):744–749

    Article  CAS  PubMed  Google Scholar 

  6. Spaderna S, Schmalhofer O, Hlubek F et al (2006) A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology 131(3):830–840

    Article  CAS  PubMed  Google Scholar 

  7. De Medina SG, Popov Z, Chopin DK et al (2008) Relationship between E-cadherin and fibroblast growth factor receptor 2b expression in bladder carcinomas. Oncogene 18:5722–5726

    Article  Google Scholar 

  8. Byrne RR, Shariat SF, Brown R et al (2001) E-cadherin immunostaining of bladder transitional cell carcinoma, carcinoma in situ and lymph node metastases with long-term followup. J Urol 165(5):1473–1479

    Article  CAS  PubMed  Google Scholar 

  9. Baumgart E, Cohen MS, Silva Neto B et al (2007) Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors. Clin Cancer Res 13(6):1685–1694

    Article  CAS  PubMed  Google Scholar 

  10. Muramaki M, Miyake H, Terakawa T, Kumano M, Sakai I, Fujisawa M (2012) Expression profile of E-cadherin and N-cadherin in non-muscle-invasive bladder cancer as a novel predictor of intravesical recurrence following transurethral resection. Urol Oncol 30(2):161–166

    Article  CAS  PubMed  Google Scholar 

  11. Clairotte A, Lascombe I, Fauconnet S, Kantelip B et al (2006) Expression of E-cadherin and alpha-, beta-, gamma-catenins in patients with bladder cancer: identification of gamma-catenin as a new prognostic marker of neoplastic progression in T1 superficial urothelial tumors. Am J Clin Pathol 125(1):119–126

    Article  CAS  PubMed  Google Scholar 

  12. Moyano Calvo JL, Blanco Palenciano E, Beato Moreno A et al (2006) Prognostic value of E-cadherina, beta catenin, Ki-67 antigen and p53 protein in the superficial bladder tumors. Actas Urol Esp 30(9):871–878

    Article  CAS  PubMed  Google Scholar 

  13. Shahin O, Thalmann GN, Rentsch C, Mazzucchelli L, Studer UE (2003) A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence, progression and survival. J Urol 169(1):96–100 discussion 100

    Article  CAS  PubMed  Google Scholar 

  14. San Miguel Fraile P, Gómez de María C, Donis Quintairos L, Carrera Vazquez A, Iglesias Martínez P, Barreiro Barbosa MJ (2007) [Expression of E-cadherin and catenins in urothelial carcinomas]. Actas Urol Esp 31(4):355–360

    Article  CAS  PubMed  Google Scholar 

  15. Jang TJ, Cha WH, Lee KS (2010) Reciprocal correlation between the expression of cyclooxygenase-2 and E-cadherin in human bladder transitional cell carcinomas. Virchows Arch 457(3):319–328

    Article  CAS  PubMed  Google Scholar 

  16. Hu X, Ruan Y, Cheng F, Yu W, Zhang X, Larré S (2011) p130Cas, E-cadherin and β-catenin in human transitional cell carcinoma of the bladder: expression and clinicopathological significance. Int J Urol 18(9):630–637

    PubMed  Google Scholar 

  17. Hurle R, Losa A, Manzetti A, Lembo A (1999) Intravesical bacillus Calmette-Guerin in stage T1, grade 3 bladder cancer therapy: a 7-year follow-up. Urology 54:258–263

    Article  CAS  PubMed  Google Scholar 

  18. Lebret T, Gaudez F, Herve JM, Barre P, Lugagne PM, Botto H (1998) Low-dose BCG instillations in the treatment of Stage T1 Grade 3 bladder tumours: recurrence, progression and success. Eur Urol 34:67–72

    Article  CAS  PubMed  Google Scholar 

  19. Orsola A, Trias I, Raventós CX et al (2005) Initial high-grade T1 urothelial cell carcinoma: feasibility and prognostic significance of lamina propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-non-treated patients. Eur Urol 48:231–238

    Article  CAS  PubMed  Google Scholar 

  20. Denzinger S, Burger M, Fritsche HM et al (2009) Prognostic value of histopathological tumour growth patterns at the invasion front of T1G3 urothelial carcinoma of the bladder. Scand J Urol Nephrol 43(4):282–287

    Article  PubMed  Google Scholar 

  21. Brake M, Loertzer H, Horsch R, Keller H (2000) Recurrence and progression of stage T1, grade 3 transitional cell carcinoma of the bladder following intravesical immunotherapy with bacillus Calmette-Guerin. J Urol 163:1697–1705

    Article  CAS  PubMed  Google Scholar 

  22. Pansadoro V, Emiliozzi P, de Paula F, Scarpone P, Pansadoro A, Sternberg CN (2002) Long-term follow-up of G3T1 transitional cell carcinoma of the bladder treated with intravesical bacille Calmette-Guerin: 18-year experience. Urology 59:227–231

    Article  PubMed  Google Scholar 

  23. Bertz S, Denzinger S, Otto W et al (2011) Histomorphological parameters can improve risk stratification in pT1 urothelial bladder cancer—evaluation of a large (hospital-based) single-centre series. Histopathology 59(4):722–732

    Article  PubMed  Google Scholar 

  24. van Rhijn BW, van der Kwast TH, Alkhateeb SS et al (2012) A new and highly prognostic system to discern t1 bladder cancer substage. Eur Urol 61(2):378–384

    Article  PubMed  Google Scholar 

  25. Bringuier PP, Umbas R, Schaafsma HE, Karthaus HF, Debruyne FM, Schalken JA (1993) Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res 53(14):3241–3245

    CAS  PubMed  Google Scholar 

  26. Kashibuchi K, Tomita K, Schalken JA, Kume H, Takeuchi T, Kitamura T (2007) The prognostic value of E-cadherin, alpha-, beta- and gamma-catenin in bladder cancer patients who underwent radical cystectomy. Int J Urol 14(9):789–794

    Article  CAS  PubMed  Google Scholar 

  27. Bryan RT, Atherfold PA, Yeo Y et al (2008) Cadherin switching dictates the biology of transitional cell carcinoma of the bladder: ex vivo and in vitro studies. J Pathol 215(2):184–194

    Article  CAS  PubMed  Google Scholar 

  28. Shi B, Laudon V, Yu S, Dong D, Zhu Y, Xu Z (2008) E-cadherin tissue expression and urinary soluble forms of E-cadherin in patients with bladder transitional cell carcinoma. Urol Int 81(3):320–324

    Article  CAS  PubMed  Google Scholar 

  29. Otto W, Denzinger S, Fritsche HM et al (2011) The WHO classification of 1973 is more suitable than the WHO classification of 2004 for predicting survival in pT1 urothelial bladder cancer. BJU Int 107(3):404–408

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Ms. Nina Nießl and Mrs. Stefanie Götz for their excellent support.

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    Authors and Affiliations

    1. Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany

      Wolfgang Otto, Johannes Breyer, Sonja Herdegen, Roman Mayr, Eva M. Lausenmeyer, Stefan Denzinger, Bas W. G. van Rhijn & Maximilian Burger

    2. Institute of Pathology, University of Regensburg, Regensburg, Germany

      Fabian Eder

    3. Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany

      Simone Bertz & Arndt Hartmann

    4. Department of Urology, Hospital St. Elisabeth, Straubing, Germany

      Matthias May

    5. Department of Surgical Oncology (Urology), Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

      Bas W. G. van Rhijn

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    1. Wolfgang Otto
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    Correspondence to Johannes Breyer.

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    Wolfgang Otto and Johannes Breyer contributed equally to this work.

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    Otto, W., Breyer, J., Herdegen, S. et al. WHO 1973 grade 3 and infiltrative growth pattern proved, aberrant E-cadherin expression tends to be of predictive value for progression in a series of stage T1 high-grade bladder cancer after organ-sparing approach. Int Urol Nephrol 49, 431–437 (2017). https://doi.org/10.1007/s11255-016-1491-9

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