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      Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

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      1 , 2 , 3 , 3 , 1 , 2 , 3 , 2 , 4 , 3 , 1 , 1 , 1 , 1 , 1 , 5 , 2 , 6 , 5 , 2 , 7 , 2 , 8 , 2 , 3 , 2 , 1 , 2 , 1 , 2 , 6 , *
      British Journal of Cancer
      Nature Publishing Group
      endoscopic ultrasound-guided fine needle aspiration, pancreatic adenocarcinoma, CA19.9, circulating tumour cells, circulating tumour DNA, solid pancreatic tumours

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          Abstract

          Background:

          The direct comparison of CA19.9, circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has never been performed for the diagnosis of solid pancreatic tumours (SPTs).

          Methods:

          We included 68 patients with a SPT referred for EUS-FNA. CTCs were analysed using size-based platform and ctDNA using digital PCR. The sensitivity, specificity, negative and positive predictive values were evaluated for each marker and their combination.

          Results:

          SPTs corresponded to 58 malignant tumours (52 pancreatic adenocarcinoma (PA) and 6 others) and 10 benign lesions. The sensitivity and specificity for PA diagnosis were 73% and 88% for EUS-FNA, 67% and 80% for CTC, 65% and 75% for ctDNA and 79% and 93% for CA19.9, respectively. The positivity of at least 2 markers was associated with a sensitivity and specificity of 78% and 91%, respectively. CtDNA was the only marker associated with overall survival (median 5.2 months for ctDNA+ vs 11.0 months for ctDNA−, P=0.01).

          Conclusions:

          CA19.9 alone and in combination with ctDNA and/or CTC analysis may represent an efficient method for diagnosing PA in patients with SPTs. Further studies including a larger cohort of patients with both malignant and benign lesions will be necessary to confirm these promising results.

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          Most cited references27

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          Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research.

          Increasing evidence suggests that circulating tumour cells (CTCs) are responsible for metastatic relapse and this has fuelled interest in their detection and quantification. Although numerous methods have been developed for the enrichment and detection of CTCs, none has yet reached the 'gold' standard. Since epithelial cell adhesion molecule (EpCAM)-based enrichment of CTCs offers several advantages, it is one of the most commonly used and has been adapted for high-throughput technology. However, emerging evidence suggests that CTCs are highly heterogeneous: they consist of epithelial tumour cells, epithelial-to-mesenchymal transition (EMT) cells, hybrid (epithelial/EMT(+)) tumour cells, irreversible EMT(+) tumour cells, and circulating tumour stem cells (CTSCs). The EpCAM-based approach does not detect CTCs expressing low levels of EpCAM and non-epithelial phenotypes such as CTSCs and those that have undergone EMT and no longer express EpCAM. Thus, the approach may lead to underestimation of the significance of CTCs, in general, and CTSCs and EMT(+) tumour cells, in particular, in cancer dissemination. Here, we provide a critical review of research literature on the evolving concept of CTCs and the inadequacy of their enrichment by EpCAM-based technology for basic and clinical cancer research. The review also outlines future perspectives in the field. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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            A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker

            Background: Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study. Patients and methods: Blood samples were obtained prospectively from 54 consenting patients and analysed by CellSearch and isolation by size of epithelial tumour cells (ISET). CellSearch exploits immunomagnetic capture of CTCs-expressing epithelial markers, whereas ISET is a marker independent, blood filtration device. Circulating tumour cell expression of epithelial and mesenchymal markers was assessed to explore any discrepancy in CTC number between the two platforms. Results: ISET detected CTCs in more patients than CellSearch (93% vs 40%) and in higher numbers (median CTCs/7.5 ml, 9 (range 0–240) vs 0 (range 0–144)). Heterogeneity observed for epithelial cell adhesion molecule, pan-cytokeratin (CK), E-Cadherin, Vimentin and CK 7 expression in CTCs may account for discrepancy in CTC number between platforms. Conclusion: ISET detects more CTCs than CellSearch and offers flexible CTC characterisation with potential to investigate CTC biology and develop biomarkers for pancreatic cancer patient management.
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              The clinical utility of the CA 19-9 tumor-associated antigen.

              Since Koprowski and coworkers discovered the CA 19-9 antigen 10 yr ago, it has become the most useful blood test in the diagnosis and management of patients with cancer of the pancreas. With an upper limit of normal of 37 U/ml, the assay's overall sensitivity is approximately 80% and its specificity is 90%. If higher cutoffs are used, the specificity rises so that, at levels greater than 1000 U/ml, the marker's specificity approaches 100%. Acute cholangitis and cirrhosis are two benign conditions that might raise this assay significantly. This tumor-associated marker is also helpful in predicting unresectability of pancreatic adenocarcinoma, as 96% of tumors that result in blood levels greater than 1000 U/ml have been found to be unresectable. After potentially curative surgery, the CA 19-9 can help prognosticate survival. Patients who normalize their CA 19-9 postoperatively live longer than those who do not. Furthermore, the assay, when used serially, predicts recurrence of disease prior to radiographic or clinical findings. The CA 19-9 is currently the "gold" standard marker for pancreatic cancer, against which other assays in this field will be judged.
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                Author and article information

                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                26 September 2017
                03 August 2017
                : 117
                : 7
                : 1017-1025
                Affiliations
                [1 ]Digestive Oncology Unit, Department of Hepatogastroenterology, Rouen University Hospital , 1 Rue de Germont, Rouen 76031, France
                [2 ]Normandie University, UNIROUEN, Inserm U1245, Team 3, IRON group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, F 76000, Rouen, France
                [3 ]Department of Pathology, Iron group, Rouen University Hospital , 1 Rue de Germont, Rouen, Cedex 76031, France
                [4 ]Department of Bio-Pathology, Henri Becquerel Center, Rue d’Amiens , Rouen 76038, France
                [5 ]Department of Surgery, Rouen University Hospital , 1 Rue de Germont, Rouen 76031, France
                [6 ]Department of Medical Oncology, Henri Becquerel Center, Rue d’Amiens , Rouen 76038, France
                [7 ]Department of Genetics, Rouen University Hospital , 1 Rue de Germont, Rouen 76031, France
                [8 ]Department of Hematology, Henri Becquerel Center, Rue d’Amiens , Rouen 76038, France
                Author notes
                [9]

                These authors contributed equally to this work.

                Article
                bjc2017250
                10.1038/bjc.2017.250
                5625666
                28772284
                1184b417-1fd4-48b8-b257-781dcbb41d39
                Copyright © 2017 Cancer Research UK

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                : 22 April 2017
                : 22 June 2017
                : 05 July 2017
                Categories
                Molecular Diagnostics

                Oncology & Radiotherapy
                endoscopic ultrasound-guided fine needle aspiration,pancreatic adenocarcinoma,ca19.9,circulating tumour cells,circulating tumour dna,solid pancreatic tumours

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