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

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 -