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 (344x clear cell [ccRCC], 63x papillary [pRCC], 18x chromophobe [chRCC]) patients in three partly overlapping cohorts. Plasma IMP3 concentrations were determined by ELISA in 98 RCC (79x ccRCC, 15x pRCC, 4x chRCC) patients and 20 controls. IMP3 mRNA expression levels were analyzed in 73 frozen tissue samples (55x ccRCC, 12x pRCC, 6x chRCC), while protein expressions were assessed in 366 FFPE samples (294x ccRCC, 56x pRCC, 16x chRCC) by 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. This article is protected by copyright. All rights reserved.
International journal of cancer. 2019 Jan 16 [Epub ahead of print]
S Tschirdewahn, A Panic, L Püllen, N N Harke, B H Hadaschik, P Riesz, A Horváth, J Szalontai, P Nyirády, H A Baba, H Reis, T Szarvas
Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany., Department of Urology, Semmelweis University, Budapest, Hungary., Institute of Pathology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.