Clinical & Experimental Metastasis

, Volume 30, Issue 2, pp 215–224 | Cite as

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

  • Edwin Herrmann
  • Carsten Weishaupt
  • Birgit Pöppelmann
  • Carina Hillgruber
  • Gerald Pühse
  • Laura Maria Krabbe
  • Micha Feld
  • Martin Steinhoff
  • Tobias Goerge
Research Paper


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.


RCC Metastasis Individual risk Prognostic marker TEER Adjuvant treatment 



Madin–Darby canine kidney cell line C7


Carbonic anhydrase IX


Endothelial cell activation


Human umbilical vein cells


Matrix metalloproteinases


Renal cell carcinoma


Transepithelial electrical resistance


Von Willebrand Factor



This study was supported by a Grant of the Interdisciplinary Center of Clinical Research (IZKF) Münster, Germany (Goe2/023/10) and the research grant GO1360/4-1 by the Deutsche Forschungsgemeinschaft.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Edwin Herrmann
    • 1
  • Carsten Weishaupt
    • 2
  • Birgit Pöppelmann
    • 2
  • Carina Hillgruber
    • 2
  • Gerald Pühse
    • 1
  • Laura Maria Krabbe
    • 1
  • Micha Feld
    • 2
  • Martin Steinhoff
    • 2
    • 3
  • Tobias Goerge
    • 2
  1. 1.Department of UrologyUniversity Hospital of MünsterMünsterGermany
  2. 2.Department of DermatologyUniversity Hospital of MünsterMünsterGermany
  3. 3.Department of DermatologyUCSFSan FranciscoUSA

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