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Claudin-1 upregulation is associated with favorable tumor features and a reduced risk for biochemical recurrence in ERG-positive prostate cancer

  • Simon Kind
  • Franziska Büscheck
  • Doris Höflmayer
  • Claudia Hube-Magg
  • Martina Kluth
  • Maria Christina Tsourlakis
  • Stefan Steurer
  • Till S. Clauditz
  • Andreas M. Luebke
  • Eike Burandt
  • Waldemar Wilczak
  • Andrea Hinsch
  • David Dum
  • Sören Weidemann
  • Christoph Fraune
  • Burkhard Beyer
  • Thomas Steuber
  • Hartwig Huland
  • Markus Graefen
  • Margit Fisch
  • Ronald SimonEmail author
  • Guido Sauter
  • Thorsten Schlomm
  • Sarah Minner
  • Till Eichenauer
Original Article
  • 32 Downloads

Abstract

Background

Claudin-1 is a membrane-tight junction protein and important for the sealing of the paracellular cleft in epithelial and endothelial cells. Differential expression of Claudin-1 is linked to disease outcome in various cancers.

Material and methods

To evaluate the potential relevance of Claudin-1 expression in prostate cancer, a tissue microarray containing samples of 17,747 tumors with annotated clinico-pathological and molecular data was immunohistochemically analyzed for Claudin-1 expression.

Results

In normal prostate, glandular cells were always Claudin-1-negative while there was a strong staining of gland-surrounding basal cells. In contrast to normal prostatic glands, a positive Claudin-1 immunostaining, was found, however, in 38.7% of 12,441 interpretable cancers and was considered weak in 12.7%, moderate in 13.2%, and strong in 12.8% of cases. Positive Claudin-1 immunostaining was associated with favorable tumor features like low pT (p = 0.0032), low Gleason grade (p< 0.0001), and a reduced risk of PSA recurrence (p = 0.0005). A positive Claudin-1 staining was markedly more frequent in ERG-positive (63%) than in ERG-negative cancers (23%; p < 0.0001). Subset analyses revealed that all associations of Claudin-1 expression and favorable phenotype and prognosis were driven by ERG-positive cancers. Multivariate analyses revealed, however, that even in ERG-positive cancers, the prognostic impact of high Claudin-1 expression was not independent of established clinico-pathological parameters. Comparison with 12 previously analyzed chromosomal deletions identified conspicuous associations with PTEN and 12p13 deletions potentially indicating functional interactions.

Conclusion

These data identify a peculiar role for Claudin-1 in prostate cancer. The protein is overexpressed in a fraction of prostate cancers and increased Claudin-1 expression levels predict a favorable prognosis in ERG-positive cancer.

Keywords

Prostate cancer Prognosis Claudin-1 Immunohistochemistry 

Notes

Acknowledgements

We are grateful to Inge Brandt, Melanie Witt, Maren Eisenberg and Sünje Seekamp for excellent technical assistance.

Author contributions

SK, TE, RS, CHM, GS: contributed to conception, design, data collection, data analysis and manuscript writing. SW, MK, DD, FB, DH, TSC, AML, EB, WW, AH, MCT, SS: conception and design, collection of samples. SK, CF, SM: immunohistochemistry analysis. TS, BB, TSt, MG, RS: collection and data analysis. TE, GS, MF: study supervision.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical standards

The usage of archived diagnostic left-over tissues for manufacturing of TMAs and their analysis for research purposes as well as patient data analysis has been approved by local laws (HmbKHG, §12,1) and by the local ethics committee (Ethics commission Hamburg, WF-049/09). All work has been carried out in compliance with the Helsinki Declaration.

Supplementary material

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Supplementary file1 (PPTX 419 kb)
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Supplementary file2 (XLSX 11 kb)
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Supplementary file3 (XLSX 11 kb)
345_2019_3017_MOESM4_ESM.xlsx (11 kb)
Supplementary file4 (XLSX 10 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Simon Kind
    • 1
  • Franziska Büscheck
    • 1
  • Doris Höflmayer
    • 1
  • Claudia Hube-Magg
    • 1
  • Martina Kluth
    • 1
  • Maria Christina Tsourlakis
    • 1
  • Stefan Steurer
    • 1
  • Till S. Clauditz
    • 1
  • Andreas M. Luebke
    • 1
  • Eike Burandt
    • 1
  • Waldemar Wilczak
    • 1
  • Andrea Hinsch
    • 1
  • David Dum
    • 1
  • Sören Weidemann
    • 1
  • Christoph Fraune
    • 1
  • Burkhard Beyer
    • 3
  • Thomas Steuber
    • 3
  • Hartwig Huland
    • 3
  • Markus Graefen
    • 3
  • Margit Fisch
    • 2
  • Ronald Simon
    • 1
    Email author
  • Guido Sauter
    • 1
  • Thorsten Schlomm
    • 4
  • Sarah Minner
    • 1
  • Till Eichenauer
    • 2
  1. 1.Institute of PathologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.Department of UrologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  3. 3.Martini-Clinic, Prostate Cancer CenterUniversity Medical Center Hamburg-EppendorfHamburgGermany
  4. 4.Department of Urology CharitéUniversitätsmedizin BerlinBerlinGermany

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