Circulating and tissue IMP3 levels are correlated with poor survival in renal cell carcinoma

Stephan Tschirdewahn, Andrej Panic, Lukas Püllen, Nina N. Harke, Boris H. Hadaschik, Peter Riesz, Andras Horváth, Janos Szalontai, P. Nyírády, Hideo A. Baba, Henning Reis, Tibor Szarvas

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusPublished - Jan 1 2019

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Renal Cell Carcinoma
Survival
Messenger RNA
Antibodies
Blood Proteins
Proteins
Multivariate Analysis
Enzyme-Linked Immunosorbent Assay
Neoplasm Metastasis
Neoplasms

Keywords

  • IMP3
  • plasma
  • prognosis
  • renal cell carcinoma
  • serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tschirdewahn, S., Panic, A., Püllen, L., Harke, N. N., Hadaschik, B. H., Riesz, P., ... Szarvas, T. (2019). Circulating and tissue IMP3 levels are correlated with poor survival in renal cell carcinoma. International Journal of Cancer. https://doi.org/10.1002/ijc.32124

Circulating and tissue IMP3 levels are correlated with poor survival in renal cell carcinoma. / Tschirdewahn, Stephan; Panic, Andrej; Püllen, Lukas; Harke, Nina N.; Hadaschik, Boris H.; Riesz, Peter; Horváth, Andras; Szalontai, Janos; Nyírády, P.; Baba, Hideo A.; Reis, Henning; Szarvas, Tibor.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Tschirdewahn, S, Panic, A, Püllen, L, Harke, NN, Hadaschik, BH, Riesz, P, Horváth, A, Szalontai, J, Nyírády, P, Baba, HA, Reis, H & Szarvas, T 2019, 'Circulating and tissue IMP3 levels are correlated with poor survival in renal cell carcinoma', International Journal of Cancer. https://doi.org/10.1002/ijc.32124
Tschirdewahn, Stephan ; Panic, Andrej ; Püllen, Lukas ; Harke, Nina N. ; Hadaschik, Boris H. ; Riesz, Peter ; Horváth, Andras ; Szalontai, Janos ; Nyírády, P. ; Baba, Hideo A. ; Reis, Henning ; Szarvas, Tibor. / Circulating and tissue IMP3 levels are correlated with poor survival in renal cell carcinoma. In: International Journal of Cancer. 2019.
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abstract = "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.",
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