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

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 c...

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Detalles Bibliográficos
Autores principales: Bernreuther, Christian, Daghigh, Ferdous, Möller, Katharina, Hube-Magg, Claudia, Lennartz, Maximilian, Lutz, Florian, Rico, Sebastian Dwertmann, Fraune, Christoph, Dum, David, Luebke, Andreas M., Eichenauer, Till, Möller-Koop, Christina, Schlomm, Thorsten, Wittmer, Corinna, Huland, Hartwig, Heinzer, Hans, Graefen, Markus, Haese, Alexander, Burandt, Eike, Tsourlakis, Maria Christina, Clauditz, Till S., Höflmayer, Doris, Izbicki, Jakob R., Simon, Ronald, Sauter, Guido, Minner, Sarah, Steurer, Stefan, Meiners, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471174/
https://www.ncbi.nlm.nih.gov/pubmed/32677026
http://dx.doi.org/10.1007/s12253-020-00861-9
Descripción
Sumario: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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12253-020-00861-9) contains supplementary material, which is available to authorized users.