Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.
Department of Urology, Semmelweis University, Budapest, Hungary.
Int J Cancer. 2019 Jul 15;145(2):531-539. doi: 10.1002/ijc.32124. Epub 2019 Jan 31.
Tissue protein expression of IMP3 is emerging as a promising prognostic factor in renal cell carcinoma (RCC). The most commonly used immunohistochemical (IHC) antibody has been criticized for its low specificity. In addition, blood levels of IMP3 have not yet been analyzed in RCC. Therefore, we compared the prognostic performance of two different IMP3 IHC antibodies and assessed the prognostic relevance of IMP3 plasma levels in RCC. IMP3 levels were assessed in an overall number of 425 RCC (344× clear cell [ccRCC], 63× papillary [pRCC], 18× chromophobe [chRCC]) patients in three partly overlapping cohorts. Plasma IMP3 concentrations were determined by ELISA in 98 RCC (79× ccRCC, 15× pRCC, 4× chRCC) patients and 20 controls. IMP3 mRNA expression levels were analyzed in 73 frozen tissue samples (55× ccRCC, 12× pRCC, 6× chRCC), while protein expressions were assessed in 366 FFPE samples (294× ccRCC, 56× pRCC, 16× chRCC) using the M3626 and N-19 antibodies. IMP3 plasma and mRNA expression levels were significantly higher in patients compared to controls and in high-grade compared to low-grade tumors. In addition, IMP3 plasma and tissue protein levels (by M3626) were higher and IMP3 mRNA expression levels tended to be higher in patients with distant metastasis. Multivariate analyses in clear cell RCC revealed high IMP3 plasma concentration and mRNA expression as independent predictors of disease-specific survival. IMP3 immunostainings by M3626 but not by N-19 were independently associated with poor overall and disease-specific survival. High plasma and tissue levels of IMP3 are independently associated with poor RCC prognosis. The applied antibody significantly impacts the prognostic performance of analysis. IMP3 analysis may improve risk-stratification of RCC patients and therefore could help to optimize therapeutic and follow-up decisions.
IMP3 的组织蛋白表达正在成为肾细胞癌 (RCC) 的一种很有前途的预后因素。最常用的免疫组织化学 (IHC) 抗体因其特异性低而受到批评。此外，IMP3 的血液水平尚未在 RCC 中进行分析。因此，我们比较了两种不同的 IMP3 IHC 抗体的预后性能，并评估了 IMP3 血浆水平在 RCC 中的预后相关性。在三个部分重叠的队列中，对总共 425 名 RCC（344×透明细胞 [ccRCC]、63×乳头状 [pRCC]、18×嫌色细胞 [chRCC]）患者的 IMP3 水平进行了评估。通过 ELISA 在 98 名 RCC（79×ccRCC、15×pRCC、4×chRCC）患者和 20 名对照者中测定了血浆 IMP3 浓度。在 73 个冷冻组织样本（55×ccRCC、12×pRCC、6×chRCC）中分析了 IMP3 mRNA 表达水平，而在 366 个 FFPE 样本（294×ccRCC、56×pRCC、16×chRCC）中使用 M3626 和 N-19 抗体评估了 IMP3 蛋白表达。与对照组相比，IMP3 血浆和 mRNA 表达水平在患者中明显升高，与高级别肿瘤相比，IMP3 血浆和 mRNA 表达水平在患者中也明显升高。此外，在远处转移的患者中，IMP3 血浆和组织蛋白水平（通过 M3626）升高，IMP3 mRNA 表达水平也升高。在 ccRCC 的多变量分析中，高 IMP3 血浆浓度和 mRNA 表达是疾病特异性生存的独立预测因子。M3626 而不是 N-19 的 IMP3 免疫染色与不良的总生存和疾病特异性生存独立相关。高血浆和组织水平的 IMP3 与不良的 RCC 预后独立相关。应用的抗体显著影响分析的预后性能。IMP3 分析可以改善 RCC 患者的风险分层，因此有助于优化治疗和随访决策。
