Clinical & Experimental Metastasis

, Volume 30, Issue 2, pp 215–224

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

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.

Keywords

RCC Metastasis Individual risk Prognostic marker TEER Adjuvant treatment 

Abbreviations

C7

Madin–Darby canine kidney cell line C7

CAIX

Carbonic anhydrase IX

ECA

Endothelial cell activation

HUVEC

Human umbilical vein cells

MMP

Matrix metalloproteinases

RCC

Renal cell carcinoma

TEER

Transepithelial electrical resistance

VWF

Von Willebrand Factor

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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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