Cancer Management and Research (2018-11-01)

Upregulation of centromere protein F is linked to aggressive prostate cancers

  • Göbel C,
  • Özden C,
  • Schroeder C,
  • Hube-Magg C,
  • Kluth M,
  • Möller-Koop C,
  • Neubauer E,
  • Hinsch A,
  • Jacobsen F,
  • Simon R,
  • Sauter G,
  • Michl U,
  • Pehrke D,
  • Huland H,
  • Graefen M,
  • Schlomm T,
  • Luebke AM

Journal volume & issue
Vol. Volume 10
pp. 5491 – 5504

Abstract

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Cosima Göbel,1,* Cansu Özden,1,* Cornelia Schroeder,2 Claudia Hube-Magg,1 Martina Kluth,1 Christina Möller-Koop,1 Emily Neubauer,1 Andrea Hinsch,1 Frank Jacobsen,1 Ronald Simon,1 Guido Sauter,1 Uwe Michl,3 Dirk Pehrke,3,4 Hartwig Huland,3 Markus Graefen,3 Thorsten Schlomm,3,4 Andreas M Luebke1 1Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 4Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany *These authors contributed equally to this work Background: Centromere protein F (CENPF) is a key component of the kinetochore complex and plays a crucial role in chromosome segregation and cell cycle progression. Recent work suggests that CENPF upregulation is linked to aggressive tumor features in a variety of malignancies including prostate cancer. Materials and methods: Using a highly annotated tissue microarray, we analyzed CENPF protein expression from a cohort of 8,298 prostatectomized patients by immunohistochemistry to study its effect on prostate-specific antigen recurrence-free survival. Results: CENPF overexpression was found in 53% of cancers, and was linked to higher Gleason grade, advanced pathological tumor stage, accelerated cell proliferation, and lymph node metastasis (p<0.0001, each). A comparison with other key molecular features accessible through the microarray revealed strong associations between CENPF overexpression and presence of erythroblast transformation-specific (ETS)-related gene (ERG) fusion as well as phosphatase and tensin homolog deletion (p<0.0001, each). CENPF overexpression was linked to early biochemical recurrence. A subset analysis revealed that this was driven by the ERG-negative subset (p<0.0001). This was independent of established preoperative and postoperative prognostic parameters in multivariate analyses. Conclusion: The results of our study identify CENPF overexpression as an important mechanism and a potential biomarker for prostate cancer aggressiveness. Keywords: CENPF, ERG, deletion, prostate cancer, tissue microarray, prognosis

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