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Molecular Medicine

, Volume 21, Issue 1, pp 371–380 | Cite as

Piwil 2 Expression Is Correlated with Disease-Specific and Progression-Free Survival of Chemotherapy-Treated Bladder Cancer Patients

  • Helge Taubert
  • Sven Wach
  • Rudolf Jung
  • Michael Pugia
  • Bastian Keck
  • Simone Bertz
  • Elke Nolte
  • Robert Stoehr
  • Jan Lehmann
  • Carsten-H. Ohlmann
  • Michael Stöckle
  • Bernd Wullich
  • Arndt Hartmann
Research Article

Abstract

Piwi-like 2 (Piwil 2) belongs to the family of Argonaute genes/proteins. The expression of Piwil 2 is associated with stem cells. A role in tumorigenesis and/or tumor progression is proposed for different cancers but not yet for bladder cancer (BCa). We investigated Piwil 2 expression by immunohistochemistry in a cohort of 202 BCa patients treated by cystectomy and adjuvant chemotherapy. The association between Piwil 2 expression and disease-specific (DSS) or progression-free survival (PFS) was calculated using Kaplan-Meier analyses and univariate/multivariate Cox regression hazard models. In a multivariate Cox regression analysis, Piwil 2 expression, either in the cytoplasm or the nucleus, was significantly associated with DSS and PFS. A weak cytoplasmic staining pattern was associated with poor DSS and tumor progression (relative risk [RR] = 2.7, P = 0.004, and RR = 2.4, P = 0.027). Likewise, absent nuclear Piwil 2 immunoreactivity was associated with poor DSS and tumor progression (RR = 2.3, P = 0.023, and RR = 2.2, P = 0.022). BCa patients whose tumors exhibited a combination of weak cytoplasmic and absent nuclear immunoreactivity had a 6-fold increased risk of tumor-related death (P = 0.005) compared with patients with strong expression. Considering only patients with high-grade G3 tumors, a 7.8-fold risk of tumor-associated death and a 3.6-fold risk of tumor progression were detected independently of the histologic tumor subtype or the chemotherapy regimen. In summary, a combination of weak cytoplasmic and absent nuclear expression of Piwil 2 is significantly associated with an increased risk of DSS and tumor progression. This indicates that Piwil 2 could be a valuable prognostic marker for high-risk BCa patients.

Notes

Acknowledgments

We would like to thank the Rudolf und Irmgard Kleinknecht-Stiftung for supporting HT, the Johannes und Frieda Marohn-Stiftung for supporting H Taubert, S Wach and E Nolte and the Dr. Robert Pfleger-Stiftung for supporting H Taubert and E Nolte. We would like to thank American Journal Experts for providing English-language editing for our manuscript.

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Authors and Affiliations

  • Helge Taubert
    • 1
  • Sven Wach
    • 1
  • Rudolf Jung
    • 2
  • Michael Pugia
    • 3
  • Bastian Keck
    • 1
  • Simone Bertz
    • 2
  • Elke Nolte
    • 1
  • Robert Stoehr
    • 2
  • Jan Lehmann
    • 4
  • Carsten-H. Ohlmann
    • 5
  • Michael Stöckle
    • 5
  • Bernd Wullich
    • 1
  • Arndt Hartmann
    • 2
  1. 1.Department of Urology, University Hospital ErlangenFriedrich-Alexander-University Erlangen-NürnbergErlangenGermany
  2. 2.Department of PathologyUniversity Hospital Erlangen, Friedrich-Alexander-University Erlangen-NürnbergErlangenGermany
  3. 3.Siemens Healthcare DiagnosticsElkhartUSA
  4. 4.Urologische Gemeinschaftspraxis, Prüner Gang and Department of UrologyStädtisches KrankenhausKielGermany
  5. 5.Department of UrologySaarland UniversityHomburgGermany

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