Clinical Research Papers:

HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy

Cristina Villares Zabalza, Meike Adam, Christoph Burdelski, Waldemar Wilczak, Corina Wittmer, Stefan Kraft, Till Krech, Stefan Steurer, Christina Koop, Claudia Hube-Magg, Markus Graefen, Hans Heinzer, Sarah Minner, Ronald Simon _, Guido Sauter, Thorsten Schlomm and Maria Christina Tsourlakis

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Oncotarget. 2015; 6:12822-12834. https://doi.org/10.18632/oncotarget.3431

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Cristina Villares Zabalza1, Meike Adam2, Christoph Burdelski3, Waldemar Wilczak1, Corina Wittmer1, Stefan Kraft1, Till Krech1, Stefan Steurer1, Christina Koop1, Claudia Hube-Magg1, Markus Graefen2, Hans Heinzer2, Sarah Minner1, Ronald Simon1, Guido Sauter1, Thorsten Schlomm2,4, Maria Christina Tsourlakis1

1Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany

2Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany

3General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany

4Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Germany

Correspondence to:

Ronald Simon, e-mail: [email protected]

Keywords: HOXB13, ERG, PTEN, TMA, prostate cancer

Received: January 16, 2015     Accepted: February 24, 2015     Published: March 23, 2015


HOXB13 is a prostate cancer susceptibility gene which shows a cancer predisposing (G84E) mutation in 0.1–0.6% of males. We analyzed the prognostic impact of HOXB13 expression by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancers. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor (AR) and prostate specific antigen (PSA) as well as molecular subtypes defined by ERG status and genomic deletions of 3p, 5q, 6q, and PTEN. HOXB13 immunostaining was detectable in 51.7% of 10,216 interpretable cancers and considered strong in 9.6%, moderate in 19.7% and weak in 22.3% of cases. HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each). The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA. Co-expression analysis identified a subset of tumors with high HOXB13 and AR but low PSA expression that had a particularly poor prognosis. HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.

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