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Epithelial–mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma

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Abstract

Purpose

To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer.

Methods

We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan–Meier analysis and uni- and multivariate Cox regression analysis.

Results

Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46 % had at least one pTa recurrence and 12 % even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71 % of patients with progression in contrast to only 40 % in cases without progression (p = 0.004). Of all progressed patients, 92 % showed overexpression of survivin in their initial pTa specimen compared to 61 % without progression (p = 0.001). Kaplan–Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p = 0.005) as well as overexpression of survivin (p = 0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p = 0.033) and multifocality (p = 0.046) and tumor size over 3 cm (p = 0.042) were prognosticators for worse PFS.

Conclusion

Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.

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Acknowledgments

The authors thank Mrs. Stefanie Götz for her excellent assistance in immunohistochemical procedures.

Author contributions

J Breyer wrote/edited the manuscript and analyzed the data; M Gierth wrote/edited the manuscript and developed the protocol/project; S Shalekenov, J Schäfer and C Giedl contributed to data collection or management; A Aziz analyzed the data; M Burger, S Denzinger and F Hofstädter developed the protocol/project; W Otto wrote/edited the manuscript, contributed to data collection or management, analyzed the data and developed the protocol/project.

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Author notes

  1. Atiqullah Aziz

    Present address: Department of Urology, University of Hamburg, Hamburg, Germany

Authors and Affiliations

  1. Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany

    Johannes Breyer, Michael Gierth, Sanzhar Shalekenov, Atiqullah Aziz, Julius Schäfer, Maximilian Burger, Stefan Denzinger & Wolfgang Otto

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

    Ferdinand Hofstädter & Christian Giedl

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  1. Johannes Breyer
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Correspondence to Johannes Breyer.

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The authors declare that they have no conflict of interest.

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For this type of study, formal consent is not required.

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Informed consent was obtained from all the individual participants included in the study.

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Johannes Breyer and Michael Gierth have contributed equally to the manuscript.

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Breyer, J., Gierth, M., Shalekenov, S. et al. Epithelial–mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma. World J Urol 34, 709–716 (2016). https://doi.org/10.1007/s00345-015-1690-5

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  • DOI: https://doi.org/10.1007/s00345-015-1690-5

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