Circulating Tumor Cell Composition in Renal Cell Carcinoma

• Published in: PloS one 2016-04, Vol.11 (4), p.e0153018-e0153018
• Main Authors: Nel, Ivonne, Gauler, Thomas C, Bublitz, Kira, Lazaridis, Lazaros, Goergens, André, Giebel, Bernd, Schuler, Martin, Hoffmann, Andreas-Claudius
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Angiogenesis; Biology and Life Sciences; Biomarkers; Biopsy; Blood; Bone marrow; Breast cancer; Cadherins; Cancer cells; Cancer metastasis; Carcinoma, Renal Cell - blood; Development and progression; Diagnosis; Experimental design; Feasibility studies; Fibroblast growth factor receptors; Fibroblasts; Fluorescent Antibody Technique; Gene expression; Gene Expression Profiling; Hep G2 Cells; Heterogeneity; Hospitals; Humans; Immunofluorescence; Invasiveness; Kidney cancer; Kidney Neoplasms - blood; Measurement; Medicine and Health Sciences; Mesenchymal stem cells; Mesenchyme; Metastases; Metastasis; Microscopy; Middle Aged; N-Cadherin; Neoplastic Cells, Circulating; Oncology; Patients; Peripheral blood; Physiological aspects; Polymerase chain reaction; Radiation therapy; Renal cell carcinoma; Research and Analysis Methods; Solid tumors; Stem cells; Subgroups; Surface markers; Tumor cells; Tumors; Vascular endothelial growth factor; Vascular endothelial growth factor receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153018

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.