Expression of MET in circulating tumor cells correlates with expression in tumor tissue from advanced-stage lung cancer patients.

Marius Ilie,Edith Szafer-Glusman,David S Shames,Véronique Hofman,Wei Yu,Julien Fayada,Elodie Long-Mira,Charles-Hugo Marquette,Elizabeth Punnoose,Catherine Butori,Rebecca Suttmann,Walter Darbonne,Salomé Lalvée,Eric Selva,Paul Hofman

doi:10.18632/oncotarget.15345

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.

Highlights

Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancers and remains a major cause of cancer death worldwide [1]
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
Baseline peripheral blood was collected from 256 advancedstage 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

Summary

INTRODUCTION

Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancers and remains a major cause of cancer death worldwide [1]. Eligibility of patients to targeted therapies relies on diagnostic assays performed on a tumor biopsy This invasive procedure is associated with a relative high risk of morbidity, and inoperable patients can be deprived from potentially more efficient therapies [23]. Circulating tumor cells (CTCs) represent an accessible, non-invasive surrogate tissue that allows access to biomarker assessment in vulnerable lung cancer patients for whom tissue biopsies are inaccessible or extremely difficult to perform and to repeat [23]. To investigate the utility of a liquid biopsy to assess a patient’s lung tumor’s MET status, here we evaluated the prevalence of MET expression in CTCs using 2 different CTC platforms, CellSearch and ISET, and compared MET expression in CTCs and matched tumor tissue in a retrospective cohort of 80 advanced-stage NSCLC patients

RESULTS

DISCUSSION

MATERIALS AND METHODS