Expression of MET in circulating tumor cells correlates with expression in tumor tissue from advanced-stage lung cancer patients
| Autor: | Eric Selva, Paul Hofman, Véronique Hofman, Wei Yu, Elodie Long-Mira, Marius Ilie, Catherine Butori, Edith Szafer-Glusman, David S. Shames, Salomé Lalvée, Julien Fayada, Rebecca Suttmann, Walter C. Darbonne, Charles-Hugo Marquette, Elizabeth Punnoose |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Adult Male medicine.medical_specialty Pathology Lung Neoplasms Gene Expression Cell Count circulating tumor cells NSCLC 03 medical and health sciences 0302 clinical medicine Circulating tumor cell immunocytochemistry Internal medicine Biopsy Biomarkers Tumor Medicine Humans Liquid biopsy Neoplasm Metastasis Lung cancer Aged Neoplasm Staging Aged 80 and over medicine.diagnostic_test business.industry Cancer Middle Aged Proto-Oncogene Proteins c-met medicine.disease Neoplastic Cells Circulating targeted therapy Immunohistochemistry Tumor Burden Clinical trial 030104 developmental biology Onartuzumab 030220 oncology & carcinogenesis Adenocarcinoma Female MET protein expression Neoplasm Grading business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Marius Ilie 1, 2, * , Edith Szafer-Glusman 3, * , Veronique Hofman 1, 2, 4 , Elodie Long-Mira 1, 2 , Rebecca Suttmann 3 , Walter Darbonne 3 , Catherine Butori 1 , Salome Lalvee 1 , Julien Fayada 4 , Eric Selva 4 , Wei Yu 3 , Charles-Hugo Marquette 5 , David S. Shames 3 , Elizabeth Punnoose 3 , Paul Hofman 1, 2, 4 1 Laboratory of Clinical and Experimental Pathology and Liquid Biopsy Laboratory, Pasteur Hospital, University Hospital Federation OncoAge, Universite Cote d’Azur, Nice, France 2 Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081/UMR CNRS 7284, Team 3, Antoine Lacassagne Cancer Center, Nice, France 3 Department of Oncology Biomarker Development and Oncology Clinical Development, Genentech, Inc, South San Francisco, California, USA 4 Nice Hospital-Related Biobank (BB 0025-00033), Pasteur Hospital, Nice, France 5 Pneumology Department, Pasteur Hospital, Nice, France * These authors contributed equally to this work Correspondence to: Paul Hofman, email: hofman.p@chu-nice.fr Keywords: MET protein expression, circulating tumor cells, NSCLC, immunocytochemistry, targeted therapy Received: June 20, 2016 Accepted: January 28, 2017 Published: February 15, 2017 ABSTRACT 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. |
| Databáze: | OpenAIRE |
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