Circulating Tumor Cell Composition in Renal Cell Carcinoma.
Due to their minimal-invasive yet potentially current character circulating tumor cells (CTC) might be useful as a "liquid biopsy" in solid tumors. However, successful application in metastatic renal cell carcinoma (mRCC) has been very limited so far. High plasticity and heterogeneity of CTC morphology challenges currently available enrichment and detection techniques with EpCAM as the usual surface marker being underrepresented in mRCC. We recently described a method that enables us to identify and characterize non-hematopoietic cells in the peripheral blood stream with varying characteristics and define CTC subgroups that distinctly associate to clinical parameters. With this pilot study we wanted to scrutinize feasibility of this approach and its potential usage in clinical studies.



Peripheral blood was drawn from 14 consecutive mRCC patients at the West German Cancer Center and CTC profiles were analyzed by Multi-Parameter Immunofluorescence Microscopy (MPIM). Additionally angiogenesis-related genes were measured by quantitative RT-PCR analysis.



We detected CTC with epithelial, mesenchymal, stem cell-like or mixed-cell characteristics at different time-points during anti-angiogenic therapy. The presence and quantity of N-cadherin-positive or CD133-positive CTC was associated with inferior PFS. There was an inverse correlation between high expression of HIF1A, VEGFA, VEGFR and FGFR and the presence of N-cadherin-positive and CD133-positive CTC.



Patients with mRCC exhibit distinct CTC profiles that may implicate differences in therapeutic outcome. Prospective evaluation of phenotypic and genetic CTC profiling as prognostic and predictive biomarker in mRCC is warranted.
Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.|ABA GmbH & Co. KG, BMZ2, Dortmund, Germany.
Ivonne
I
Nel
Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.|Department of Radiotherapy, University of Duisburg-Essen, Essen, Germany.
Thomas C
TC
Gauler
Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
Kira
K
Bublitz
Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
Lazaros
L
Lazaridis
Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
André
A
Goergens
Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Bernd
B
Giebel
Department of Radiotherapy, University of Duisburg-Essen, Essen, Germany.|Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
Martin
M
Schuler
Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.|Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
Andreas-Claudius
AC
Hoffmann
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000097:blood*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D056945:Hep G2 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood*; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating