New tools for assessing the individual risk of metastasis in renal cell carcinoma.
Clin Exp Metastasis
; 30(2): 215-24, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-22915161
Localized renal cell carcinoma (RCC) progresses to metastatic 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endothelium, Vascular
/
Carcinoma, Renal Cell
/
Electric Impedance
/
Epithelial Cells
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Kidney Neoplasms
/
Melanoma
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Exp Metastasis
Journal subject:
NEOPLASIAS
Year:
2013
Document type:
Article
Affiliation country:
Germany
Country of publication:
Netherlands