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      High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness

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          Abstract

          Circulating tumors cells ( CTCs) can be detected in the blood of metastatic melanoma patients ( MMPs) both as isolated circulating tumor cells ( iCTCs) and circulating tumor microemboli ( CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell ( ISET) method. We characterized the phenotype of CTCs using anti‐ PS100, anti‐ SOX10, anti‐ CD10, and anti‐ TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow‐up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs.

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          Most cited references27

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          Circulating tumor cells: liquid biopsy of cancer.

          The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with >400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include (a) estimation of the risk for metastatic relapse or metastatic progression (prognostic information), (b) stratification and real-time monitoring of therapies, (c) identification of therapeutic targets and resistance mechanisms, and (d) understanding metastasis development in cancer patients. This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecular-characterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelial-mesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells). A considerable number of promising CTC-detection techniques have been developed in recent years. The analytical specificity and clinical utility of these methods must be demonstrated in large prospective multicenter studies to reach the high level of evidence required for their introduction into clinical practice. © 2012 American Association for Clinical Chemistry
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            Molecular analysis of circulating tumour cells-biology and biomarkers.

            Growing evidence for intratumour heterogeneity informs us that single-site biopsies fall short of revealing the complete genomic landscape of a tumour. With an expanding repertoire of targeted agents entering the clinic, screening tumours for genomic aberrations is increasingly important, as is interrogating the tumours for resistance mechanisms upon disease progression. Multiple biopsies separated spatially and temporally are impractical, uncomfortable for the patient and not without risk. Here, we describe how circulating tumour cells (CTCs), captured from a minimally invasive blood test-and readily amenable to serial sampling-have the potential to inform intratumour heterogeneity and tumour evolution, although it remains to be determined how useful this will be in the clinic. Technologies for detecting and isolating CTCs include the validated CellSearch(®) system, but other technologies are gaining prominence. We also discuss how recent CTC discoveries map to mechanisms of haematological spread, previously described in preclinical models, including evidence for epithelial-mesenchymal transition, collective cell migration and cells with tumour-initiating capacity within the circulation. Advances in single-cell molecular analysis are enhancing our ability to explore mechanisms of metastasis, and the combination of CTC and cell-free DNA assays are anticipated to provide invaluable blood-borne biomarkers for real-time patient monitoring and treatment stratification.
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              Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer.

              Trials in castration-resistant prostate cancer (CRPC) need new clinical end points that are valid surrogates for survival. We evaluated circulating tumor cell (CTC) enumeration as a surrogate outcome measure.
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                Author and article information

                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                06 March 2016
                June 2016
                : 5
                : 6 ( doiID: 10.1002/cam4.2016.5.issue-6 )
                : 1022-1030
                Affiliations
                [ 1 ] Institute for Research on Cancer and Aging in Nice (IRCAN) INSERM U1081/CNRS UMR7284University of Nice Sophia Antipolis Antoine Lacassagne Cancer Center NiceFrance
                [ 2 ] Laboratory of Clinical and Experimental PathologyPasteur Hospital NiceFrance
                [ 3 ] Human BiobankPasteur Hospital BB‐0033‐00025 NiceFrance
                [ 4 ] Department of SurgeryComprehensive Cancer Center Antoine Lacassagne NiceFrance
                [ 5 ] Department of DermatologyArchet II Hospital NiceFrance
                [ 6 ] INSERM U1065 Team 1University of Nice Sophia Antipolis Equipe Labellisée Ligue 2013 NiceFrance
                [ 7 ] Unit of GeneticsArchet Hospital NiceFrance
                [ 8 ]Cancer Research Association (ARC) Labelled Team VillejuifFrance
                [ 9 ]“OncoAge” Hospital‐University Federation CHU NiceFrance
                Author notes
                [*] [* ] Correspondence

                Paul Hofman, Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, 30 Voie Romaine, 06001 Nice Cedex 01, France. Tel: +33 4 92 03 87 49; Fax: + 33 4 92 03 87 50; E‐mail: hofman.p@ 123456chu-nice.fr

                [†]

                These authors contributed equally to this work.

                Article
                CAM4661
                10.1002/cam4.661
                4924359
                26945789
                1768fba2-a8a2-4aea-8dd3-6ca5c75e92bb
                © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 July 2015
                : 12 January 2016
                : 13 January 2016
                Page count
                Pages: 9
                Funding
                Funded by: French Government (National Research Agency, ANR)
                Award ID: ANR‐11‐LABX‐0028‐01
                Funded by: Fondation ARC pour la recherche sur le cancer
                Award ID: ARC SL220110603478
                Funded by: Canceropole PACA and Region PACA (France)
                Categories
                Original Research
                Clinical Cancer Research
                Original Research
                Custom metadata
                2.0
                cam4661
                June 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.1 mode:remove_FC converted:28.06.2016

                Oncology & Radiotherapy
                circulating tumor cells,circulating tumor microemboli,immunocytochemistry,metastatic melanoma,prognosis

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