Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions.

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.

• Authors: Christian Bernreuther, Ferdous Daghigh, Katharina Möller, Claudia Hube-Magg, Maximilian Lennartz, Florian Lutz, Sebastian Dwertmann Rico, Christoph Fraune, David Dum, Andreas M Luebke, Till Eichenauer, Christina Möller-Koop, Thorsten Schlomm, Corinna Wittmer, Hartwig Huland, Hans Heinzer, Markus Graefen, Alexander Haese, Eike Burandt, Maria Christina Tsourlakis, Till S Clauditz, Doris Höflmayer, Jakob R Izbicki, Ronald Simon, Guido Sauter, Sarah Minner, Stefan Steurer, Jan Meiners
• Journal: Pathology oncology research : POR (Pathol Oncol Res) Vol. 26 Issue 4 Pg. 2709-2722 (Oct 2020) ISSN: 1532-2807 [Electronic] Switzerland
• PMID: 32677026 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• ERG protein, human
• Oncogene Proteins, Fusion
• Proto-Oncogene Proteins
• SFRP4 protein, human
• Transcriptional Regulator ERG
• Serine Endopeptidases
• TMPRSS2 protein, human
• Prostate-Specific Antigen

Topics

• Aged
• Biomarkers, Tumor (genetics, metabolism)
• Case-Control Studies
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Oncogene Proteins, Fusion (genetics)
• Prognosis
• Prostate-Specific Antigen
• Prostatectomy
• Prostatic Neoplasms (genetics, metabolism, pathology, surgery)
• Proto-Oncogene Proteins (genetics, metabolism)
• Serine Endopeptidases (genetics)
• Survival Rate
• Tissue Array Analysis
• Transcriptional Regulator ERG (genetics)