Research Paper

Clinical & Experimental Metastasis

, Volume 30, Issue 2, pp 215-224

First online:

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

  • Edwin HerrmannAffiliated withDepartment of Urology, University Hospital of Münster
  • , Carsten WeishauptAffiliated withDepartment of Dermatology, University Hospital of Münster
  • , Birgit PöppelmannAffiliated withDepartment of Dermatology, University Hospital of Münster
  • , Carina HillgruberAffiliated withDepartment of Dermatology, University Hospital of Münster
  • , Gerald PühseAffiliated withDepartment of Urology, University Hospital of Münster
  • , Laura Maria KrabbeAffiliated withDepartment of Urology, University Hospital of Münster
  • , Micha FeldAffiliated withDepartment of Dermatology, University Hospital of Münster
  • , Martin SteinhoffAffiliated withDepartment of Dermatology, University Hospital of MünsterDepartment of Dermatology, UCSF
  • , Tobias GoergeAffiliated withDepartment of Dermatology, University Hospital of Münster Email author 

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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