Expression of MET in circulating tumor cells correlates with expression in tumor tissue from advanced-stage lung cancer patients
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Marius Ilie1,2,*, Edith Szafer-Glusman3,*, Véronique Hofman1,2,4, Elodie Long-Mira1,2, Rebecca Suttmann3, Walter Darbonne3, Catherine Butori1, Salomé Lalvée1, Julien Fayada4, Eric Selva4, Wei Yu3, Charles-Hugo Marquette5, David S. Shames3, Elizabeth Punnoose3, Paul Hofman1,2,4
1Laboratory of Clinical and Experimental Pathology and Liquid Biopsy Laboratory, Pasteur Hospital, University Hospital Federation OncoAge, Université Côte d’Azur, Nice, France
2Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081/UMR CNRS 7284, Team 3, Antoine Lacassagne Cancer Center, Nice, France
3Department of Oncology Biomarker Development and Oncology Clinical Development, Genentech, Inc, South San Francisco, California, USA
4Nice Hospital-Related Biobank (BB 0025-00033), Pasteur Hospital, Nice, France
5Pneumology Department, Pasteur Hospital, Nice, France
*These authors contributed equally to this work
Paul Hofman, email: firstname.lastname@example.org
Keywords: MET protein expression, circulating tumor cells, NSCLC, immunocytochemistry, targeted therapy
Received: June 20, 2016 Accepted: January 28, 2017 Published: February 15, 2017
Given the difficulty in obtaining adequate tissue in NSCLC, we investigated the utility of circulating tumor cells (CTCs) for MET status assessment in NSCLC patients. We used two platforms for CTC capture, and assessed MET expression in CTCs and matched-bronchial biopsies in patients with advanced-stage III/IV lung adenocarcinoma. Baseline peripheral blood was collected from 256 advanced-stage III/IV NSCLC patients from Genentech clinical trials, and from 106 patients with advanced-stage III/IV lung adenocarcinoma treated at the Department of Pneumology, Pasteur Hospital, Nice. CTCs were enriched using CellSearch (Genentech), or ISET technologies (Pasteur Hospital). MET expression was evaluated by immunofluorescence on CellSearch, and by immunocytochemistry on ISET-enriched CTCs and on matched FFPE tissue sections (Pasteur Hospital). CTCs were detected in 83 of 256 (32%) patients evaluated on CellSearch, with 30 samples (12%) exhibiting ≥ 5 CTCs/7.5 ml blood. On ISET, CTC were observed in 80 of 106 patients (75%), and 79 patients (75%) exhibited ≥ 5 CTCs/4 ml blood. MET expression on ISET CTCs was positive in 72% of cases, and the MET expression on matched-patient tissue was positive in 65% patients using the Onartuzumab IHC scoring algorithm (93% concordance). Quantification of MET expression using H-scores showed strong correlation between MET expression in tissue and CTCs (Spearman correlation, 0.93). MET status in CTCs isolated on ISET filters from blood samples of advanced-stage NSCLC patients correlated strongly with MET status in tumor tissue, illustrating the potential for using CTCs as a non-invasive, real-time biopsy to determine MET status of patients entering clinical trials.
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