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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

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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.

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Acknowledgements

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

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Authors and Affiliations

  1. Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    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, Ronald Simon, Guido Sauter & Sarah Minner

  2. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Margit Fisch & Till Eichenauer

  3. Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Burkhard Beyer, Thomas Steuber, Hartwig Huland & Markus Graefen

  4. Department of Urology Charité, Universitätsmedizin Berlin, Berlin, Germany

    Thorsten Schlomm

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  1. Simon Kind
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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.

Corresponding author

Correspondence to Ronald Simon.

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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.

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Kind, S., Büscheck, F., Höflmayer, D. et al. Claudin-1 upregulation is associated with favorable tumor features and a reduced risk for biochemical recurrence in ERG-positive prostate cancer. World J Urol 38, 2185–2196 (2020). https://doi.org/10.1007/s00345-019-03017-w

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