Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG
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ORIGINAL ARTICLE
Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions Christian Bernreuther 1 & Ferdous Daghigh 1 & Katharina Möller 1 & Claudia Hube-Magg 1 & Maximilian Lennartz 1 & Florian Lutz 1 & Sebastian Dwertmann Rico 1 & Christoph Fraune 1 & David Dum 1 & Andreas M. Luebke 1 & Till Eichenauer 2 & Christina Möller-Koop 1 & Thorsten Schlomm 3 & Corinna Wittmer 1 & Hartwig Huland 4 & Hans Heinzer 4 & Markus Graefen 4 & Alexander Haese 4 & Eike Burandt 1 & Maria Christina Tsourlakis 1 & Till S. Clauditz 1 & Doris Höflmayer 1 & Jakob R. Izbicki 5 & Ronald Simon 1 & Guido Sauter 1 & Sarah Minner 1 & Stefan Steurer 1 & Jan Meiners 5 Received: 13 February 2020 / Accepted: 23 June 2020 # The Author(s) 2020
Abstract Secreted frizzled-related protein 4 (SFRP4) controls WNT signaling and is thought to play a role for tumor aggressiveness. Here, we analyzed a tissue microarray containing 11,152 prostate cancers with pathological, clinical and molecular data by immunohistochemistry. SFRP4 expression was higher in cancer than in non-neoplastic acinar cells. SFRP4 staining was seen in 64.9% of tumors and classified as weak in 33.2%, moderate in 23.9% and strong in 7.8% of cancers. SFRP4 overexpression was linked to advanced tumor stage, high classical/quantitative Gleason grade (p < 0.0001 each), lymph node metastasis (p = 0.0002), and a positive surgical margin (p = 0.0017). SFRP4 positivity was markedly more frequent in ERG positive (77.4%) than in ERG negative cancers (57.4% p < 0.0001). Subset analyses in 2725 cancers with and 3592 cancers without TMPRSS2:ERG fusion revealed that associations with tumor phenotype and patient outcome were largely driven by the subset of ERG negative tumors. In a multivariate analysis including various postoperative and prognostic clinico-pathological features, SFRP4 protein expression emerged as an independent prognostic parameter in ERG negative cancers. SFRP4 immunostaining was significantly linked with 10 of 11 previously analyzed chromosomal deletions (p < 0.05 each). In conclusion, high SFRP4 immunostaining is associated with poor prognosis and genomic instability in ERG negative prostate cancers. Keywords SFRP4 . Prognosis . Prostate cancer . TMA Christian Bernreuther and Ferdous Daghigh contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12253-020-00861-9) contains supplementary material, which is available to authorized users. * Ronald Simon [email protected] 1
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr, 52, 20246 Hamburg, Germany
2
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
3
Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany
4
Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
5
General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Ha
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