Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions
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Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions. / 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.
in: PATHOL ONCOL RES, Jahrgang 26, Nr. 4, 10.2020, S. 2709-2722.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions
AU - Bernreuther, Christian
AU - Daghigh, Ferdous
AU - Möller, Katharina
AU - Hube-Magg, Claudia
AU - Lennartz, Maximilian
AU - Lutz, Florian
AU - Rico, Sebastian Dwertmann
AU - Fraune, Christoph
AU - Dum, David
AU - Luebke, Andreas M
AU - Eichenauer, Till
AU - Möller-Koop, Christina
AU - Schlomm, Thorsten
AU - Wittmer, Corinna
AU - Huland, Hartwig
AU - Heinzer, Hans
AU - Graefen, Markus
AU - Haese, Alexander
AU - Burandt, Eike
AU - Tsourlakis, Maria Christina
AU - Clauditz, Till S
AU - Höflmayer, Doris
AU - Izbicki, Jakob R
AU - Simon, Ronald
AU - Sauter, Guido
AU - Minner, Sarah
AU - Steurer, Stefan
AU - Meiners, Jan
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
U2 - 10.1007/s12253-020-00861-9
DO - 10.1007/s12253-020-00861-9
M3 - SCORING: Journal article
C2 - 32677026
VL - 26
SP - 2709
EP - 2722
JO - PATHOL ONCOL RES
JF - PATHOL ONCOL RES
SN - 1219-4956
IS - 4
ER -