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.

分泌的卷曲相关蛋白4（SFRP4）控制WNT信号传导，并被认为在肿瘤侵袭中起作用。在这里，我们通过免疫组织化学分析了包含11,152例前列腺癌的组织芯片，​​并具有病理，临床和分子数据。SFRP4在癌症中的表达高于非肿瘤腺泡细胞。SFRP4染色在64.9％的肿瘤中可见，分类为弱33.2％，中度23.9％和强7.8％。SFRP4过表达与晚期肿瘤，高经典/定量格里森分级（ 每个p <0.0001），淋巴结转移（p  = 0.0002）和手术切缘阳性有关（p = 0.0017）。SFRP4阳性率在ERG阳性（77.4％）中比在ERG阴性癌症（57.4％p  <0.0001）中更为明显。在2725例有TMPRSS2：ERG融合的癌症和3592例无TMPRSS2：ERG融合的癌症中的亚组分析显示，与肿瘤表型和患者预后的相关性在很大程度上是由ERG阴性肿瘤的子集驱动的。在包括各种术后和预后临床病理特征的多变量分析中，SFRP4蛋白表达已成为ERG阴性癌症的独立预后参数。SFRP4免疫染色与先前分析的11个染色体缺失中的10个显着相关（p 每个<0.05）。总之，高SFRP4免疫染色与ERG阴性前列腺癌的不良预后和基因组不稳定有关。