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Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer

Goltz, Diane1; Montani, Matteo2; Braun, Martin1; Perner, Sven3; Wernert, Nicolas1; Jung, Klaus4,5; Dietel, Manfred6; Stephan, Carsten4,5; Kristiansen, Glen1

Pathology - Journal of the RCPA: December 2015 - Volume 47 - Issue 7 - p 629–636
doi: 10.1097/PAT.0000000000000320

Summary: We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.

PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan–Meier statistics.

In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16–3.63%) and 0.0152% (95%CI 0.0112–0.0191%), respectively.

Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.

As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG− or AR+).

1Institute of Pathology, University of Bonn, Germany

2Institute of Pathology, University of Bern, Switzerland

3Institute of Pathology, Section for Prostate Cancer Research, University of Bonn

4Department of Urology, Charité - Universitätsmedizin Berlin, Berlin

5Berlin Institute for Urologic Research, Berlin

6Institute of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany

Address for correspondence: Glen Kristiansen, MD, Institute of Pathology of the University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany. E-mail:

Received 4 April, 2015

Revised 11 June, 2015

Accepted 19 June, 2015

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© 2015 Royal College of Pathologists of Australasia
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