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01-02-2013 | Research Paper

New tools for assessing the individual risk of metastasis in renal cell carcinoma

Authors: Edwin Herrmann, Carsten Weishaupt, Birgit Pöppelmann, Carina Hillgruber, Gerald Pühse, Laura Maria Krabbe, Micha Feld, Martin Steinhoff, Tobias Goerge

Published in: Clinical & Experimental Metastasis | Issue 2/2013

Abstract

Localized renal cell carcinoma (RCC) progresses to metastastic disease in 20–40 % after surgical resection. Affected patients might benefit from adjuvant treatment and have to be reliably identified for treatment indication. However, existing molecular markers and classification nomograms lack sufficient validity for clinical application so far. Therefore, in order to improve diagnostic tools for the identification of patients at risk, we tested invasiveness and the capability to activate vascular endothelium of primary RCC cells as tumor specific functional parameters. As a parameter for cell invasiveness the ability of RCC cells to break-down transepithelial electrical resistance (TEER) of an epithelial cell monolayer was tested. Loss of resistance, calculated as invasivity index, resembled the degree of cell invasiveness. In addition, secretion of Von Willebrand Factor by endothelial cells incubated with RCC cell supernatant was measured as a surrogate marker for endothelial cell activation. TEER-assay results matched clinical status of disease in 9 out of 12 cases. Metastatic tumors and less differentiated tumors had a significant increase of invasivity index (p = 0.007; p = 0.034). Endothelial cell activation and clinical outcome matched in 5 out of 9 samples. In addition, tumor cell induced endothelial cell activation significantly correlated to the pathologic T classification status of RCC tumors (p = 0.009). Taken together, our study validated endothelial cell activation analysis and cell invasiveness as solitary prognostic markers for tumor dissemination. TEER-analysis has proven to be a useful functional assay giving highly relevant individual information on functional tumor cell characteristics that add to pathologic evaluation.

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Title: New tools for assessing the individual risk of metastasis in renal cell carcinoma
Authors: Edwin Herrmann
Carsten Weishaupt
Birgit Pöppelmann
Carina Hillgruber
Gerald Pühse
Laura Maria Krabbe
Micha Feld
Martin Steinhoff
Tobias Goerge
Publication date: 01-02-2013
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 2/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-012-9529-6

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