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2016 ; 11
(4
): e0153018
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Circulating Tumor Cell Composition in Renal Cell Carcinoma
#MMPMID27101285
Nel I
; Gauler TC
; Bublitz K
; Lazaridis L
; Goergens A
; Giebel B
; Schuler M
; Hoffmann AC
PLoS One
2016[]; 11
(4
): e0153018
PMID27101285
show ga
PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
RESULTS: 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. CONCLUSIONS: 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.
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