Research Paper Volume 11, Issue 18 pp 7859—7879

Up regulation of Rho-associated coiled-coil containing kinase1 (ROCK1) is associated with genetic instability and poor prognosis in prostate cancer

Stefan Steurer 1, *, , Benjamin Hager 1, *, , Franziska Büscheck 1, , Doris Höflmayer 1, , Maria Christina Tsourlakis 1, , Sarah Minner 1, , Till S. Clauditz 1, , Claudia Hube-Magg 1, , Andreas M. Luebke 1, , Ronald Simon 1, , Jakob R. Izbicki 2, , Eike Burandt 1, , Guido Sauter 1, , Christoph Fraune 1, , Sören Weidemann 1, , Thorsten Schlomm 4, , Hans Heinzer 3, , Alexander Haese 3, , Markus Graefen 3, , Hartwig Huland 3, , Asmus Heumann 2, ,

  • 1 Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 2 General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 3 Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 4 Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany
* Equal contribution

received: July 4, 2019 ; accepted: September 14, 2019 ; published: September 25, 2019 ;

https://doi.org/10.18632/aging.102294
How to Cite

Copyright © 2019 Steurer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background and objectives: Overexpression of the cytoskeleton-modulating kinase ROCK1 has been associated with unfavorable outcome in many cancers, but its impact in prostate cancer is largely unknown.

Results: A weak ROCK1 staining was found in >90% of normal, and cancerous prostate tissues, but was generally stronger in cancer cells as compared to adjacent normal glands. In cancer, ROCK1 staining was considered weak, moderate, and strong in 22%, 53%, and 18% of cases respectively. Higher ROCK1 expression levels were associated with tumor stage, and Gleason grade, positive nodal stage, positive surgical margin, accelerated cell proliferation and early PSA recurrence in multivariable analysis. ROCK1 up regulation was associated with androgen receptor (AR) expression, TMPRSS2:ERG fusion, genomic deletions of the PTEN tumor suppressor, as well as recurrent deletions at chromosomes 3p, 5q, 6q. Strong ROCK1 staining was found in 3% of AR-negative, but in 27% of strongly AR positive cancers, in 13% of ERG-negative but in 25% of ERG positive cancers, and in 12% of PTEN normal but in 26% of PTEN deleted cancers.

Conclusions: This study identifies ROCK1 expression associated with prognosis in prostate cancer.

Methods: We tested ROCK1 expression in 12 427 prostate cancer specimens and followed PSA recurrence after prostatectomy.

Abbreviations

AR: Androgen receptor; ERG: ETS-related gene; ETS: E26 transformation-specific; PSA: Prostate specific antigen; PTEN: Phosphatase and Tensin homolog; ROCK1: Rho-associated coiled containing kinase 1; TMA: Tissue microarray; TMPRSS2: Transmembrane protease, serine 2; UICC: International Union Against Cancer.