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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Volume 56, Issue 6

Issues

Use of circulating tumor cells in prospective clinical trials for NSCLC patients – standardization of the pre-analytical conditions

Marius IlieORCID iD: http://orcid.org/0000-0002-2014-1236
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology and Liquid Biopsy Laboratory, Nice, France
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Hospital-Integrated Biobank (BB-0033-00025), Nice, France
  • Université Côte d’Azur, CHU de Nice, Institute of Research on Cancer and Ageing of Nice (IRCAN), Inserm U1081, CNRS UMR7284, Team 4, Nice, France
  • orcid.org/0000-0002-2014-1236
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/ Véronique Hofman
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology and Liquid Biopsy Laboratory, Nice, France
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Hospital-Integrated Biobank (BB-0033-00025), Nice, France
  • Université Côte d’Azur, CHU de Nice, Institute of Research on Cancer and Ageing of Nice (IRCAN), Inserm U1081, CNRS UMR7284, Team 4, Nice, France
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/ Sylvie Leroy
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Department of Pulmonary Medicine and Oncology, Nice, France
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/ Charlotte Cohen
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Department of Thoracic Surgery, Nice, France
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/ Simon Heeke
  • Université Côte d’Azur, CHU de Nice, Institute of Research on Cancer and Ageing of Nice (IRCAN), Inserm U1081, CNRS UMR7284, Team 4, Nice, France
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/ Florian Cattet
  • Université Côte d’Azur, CHU de Nice, Department of Anesthesiology and Critical Care, Nice, France
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/ Coraline Bence
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology and Liquid Biopsy Laboratory, Nice, France
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/ Salomé Lalvée
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology and Liquid Biopsy Laboratory, Nice, France
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/ Jérôme Mouroux
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Department of Thoracic Surgery, Nice, France
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/ Charles-Hugo Marquette
  • Université Côte d’Azur, CHU de Nice, Institute of Research on Cancer and Ageing of Nice (IRCAN), Inserm U1081, CNRS UMR7284, Team 4, Nice, France
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Department of Pulmonary Medicine and Oncology, Nice, France
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/ Paul Hofman
  • Corresponding author
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology and Liquid Biopsy Laboratory, Nice, France
  • Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Hospital-Integrated Biobank (BB-0033-00025), Nice, France
  • Université Côte d’Azur, CHU de Nice, Institute of Research on Cancer and Ageing of Nice (IRCAN), Inserm U1081, CNRS UMR7284, Team 4, Nice, France
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Published Online: 2018-02-03 | DOI: https://doi.org/10.1515/cclm-2017-0764

Abstract

Background:

Circulating tumor cells (CTCs) hold potential for noninvasive diagnosis, prognosis and prediction testing in non-small cell lung cancer (NSCLC) patients. Minimizing degradation or loss of CTCs is pivotal for detection and profiling of the low abundance and fragile CTCs, particularly in clinical trials. We prospectively investigated (NCT02372448) whether a new blood collection device performed better compared to commonly used K3EDTA tubes, when subjected to long-term sample storage.

Methods:

Blood samples were drawn into K3EDTA and blood collection tubes (BCT) (Streck), and filtered by the Isolation by SizE of Tumor/Trophoblastic Cells (ISET® system), for CTC detection in two study populations of NSCLC patients; the training set of 14 patients with stage II/IV NSCLC, and the validation set of 36 patients with stage IV NSCLC). MET expression was evaluated by immunocytochemistry (ICC) and anaplastic lymphoma kinase (ALK) gene rearrangement by break-apart fluorescence in situ hybridization (FISH) on ISET-enriched CTCs.

Results:

Blood processed after 24 h and 48 h in BCT tubes showed stable CTCs counts and integrity, whereas CTCs in K3EDTA tubes showed an altered morphology in all patients. CTCs recovered in BCT or K3EDTA tubes at 24 and 48 h were evaluable by ICC for MET expression and by FISH for ALK rearrangement.

Conclusions:

The BCT tubes gave a high yield and preserved the integrity of CTCs after 24 and 48 h of storage at room temperature, which facilitate their molecular characterization in NSCLC patients entering clinical trials.

This article offers supplementary material which is provided at the end of the article.

Keywords: BCT; circulating tumor cells; Isolation by SizE of Tumor/Trophoblastic Cells (ISET); K3EDTA; non-small cell lung cancer (NSCLC); stability

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About the article

Corresponding author: Prof. Paul Hofman, Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology and Liquid Biopsy Laboratory, Pasteur Hospital, BP69, 06001 Nice Cedex, France, Phone: +33 4 92 03 88 55, Fax: +33 4 92 03 88 50

aMembers of the AIR project Study Group: Dominique Israel-Biet MD (Hôpital Européen Georges Pompidou), Christophe Pison MD (Hôpital Universitaire de Grenoble), Pascal Chanez MD (Hôpital Universitaire de Marseille), Francois Chabot MD (Hôpital Universitaire de Nancy), Gaetan Deslee MD (Hôpital Universitaire de Reims), Hervé Mal MD (Hôpital Bichat), Romain Kessler MD (Hôpital Universitaire de Strasbourg), Jean-Michel Vergnon MD, Isabelle Pelissier MD (Hôpital Universitaire de St Etienne), Antoine Cuvelier MD (Hôpital Universitaire de Rouen), Arnaud Bourdin MD (Hôpital Universitaire de Montpellier), Vincent Jounieaux MD (Hôpital Universitaire d’Amiens), Nicolas Roche MD (Hôpital Cochin), Stephane Jouneau MD (Hôpital Universitaire de Rennes), Philippe Bonniaud MD (Hôpital Universitaire de Dijon), Arnaud Scherpereel MD (Hôpital Universitaire de Lille), Jean Francois Mornex MD (Hôpital Universitaire de Lyon), Francois Steenhouwer MD (Hôpital de Roubaix), Sylvie Leroy MD, Charles Hugo Marquette MD, Jonathan Benzaquen, Andrea Mazzette MD, Bernard Padovani MD, Paul Hofman MD, Marius Ilie MD, Veronique Hofman MD, Johanna Pradelli MD, Maureen Fontaine, Jennifer Griffonnet, Ariane Guillemart, Catherine Butori MD, Eric Selva, (Hôpital Universitaire de Nice), Sylvain Marchand-Adam MD, Laurent Plantier, Gaelle Fajolle, Melanie Rayez (Hôpital Universitaire de Tours), Jacques Cadranel MD, Vincent Falle MD, Nouha Chaabane MD, Anne Marie Ruppert MD (Hôpital Tenon), Julien Mazières MD, Damien Rouviere MD, Emilie Bousquet MD (Hôpital Universitaire de Toulouse).


Received: 2017-08-26

Accepted: 2017-12-26

Published Online: 2018-02-03

Published in Print: 2018-05-24


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: STALKLUNG01 (Institut National du Cancer, PHRC National Cancer 2014-A00417-40, Funder Id: 10.13039/501100006364), Cancéropôle PACA, Ligue départementale 06, Conseil départemental 06 Appel à projet santé.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 6, Pages 980–989, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0764.

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