Abstract 1580: MET expression in circulating tumor cells (CTCs) isolated on the ISET platform correlates with MET expression in matched tumor tissue in advanced NSCLC patients
Authors: Ilie Marius , Szafer-Glusman Edith , Hofman Veronique , Suttman Rebecca , Darbonne Walter , Marquette Charles-Hugo , Shames David S. , Punnoose Elizabeth , Hofman Paul 
Published: August 2015

Abstract
Background: Overexpression of the MET receptor tyrosine kinase is frequent in lung cancers and is associated with poor prognosis. Recent clinical studies of MET targeted therapies have used immunohistochemistry (IHC) in tissue biopsies to evaluate MET protein expression. Due to the difficulty in obtaining adequate tissue in diseases such as NSCLC, we investigated the utility of circulating tumor cells (CTCs) as a non-invasive method to evaluate MET status in NSCLC patients. We compared two platforms for CTC capture, CellSearch and ISET, and assessed MET expression in CTCs vs. matched bronchial biopsies in patients with advanced-stage III/IV lung adenocarcinoma
Design: CTC capture and MET expression in CTCs was evaluated in 358 MET positive NSCLC patients (Phase III OAM4971 trial) using the CellSearch platform. CTC capture and MET expression was evaluated in a cohort of 80 CTC-positive NSCLC patients using the ISET platform (filtration). MET was detected in CellSearch-captured CTCs by immunofluorescence using the 15A5 mouse monoclonal antibody (Genentech), and in ISET-captured CTCs and FFPE tissue sections by immunohistochemistry using the SP44 c-MET antibody from Ventana Medical Systems, Tucson, USA. Both reagents performed equally on the CellSearch platform.
Results: CTCs were detected in 108 of 358 (30%) patients evaluated on CellSearch, with CTC enumeration ranging from 0 to 193 CTCs/7.5 ml blood, and median 0 CTCs/7.5ml blood. Although OAM4971 patients were selected for positive MET expression in tissue, we failed to detect MET expression in most CTCs isolated by CellSearch, with 75% patients showing CTC H-score &lt; 15. On the ISET platform, CTCs enumeration ranged from 2 to 268 CTCs/ml, with median 65 CTCs/ml. Clusters of CTCs were observed in 93% of patients, exhibiting between 1 to 23-clusters/ml blood. The MET assay on CTCs was positive in 54 of 75 (72%) patients, and the MET assay on tissue was positive in 46 of 75 (62%) patients using the onartuzumab IHC scoring algorithm*, with MET status in CTCs concordant with status in patient-matched tumor tissue.
Conclusion: Based on our data, CTCs enumeration and MET status on CTCs from NSCLC patients captured and evaluated on the ISET system were more successful than on the CellSearch platform. On ISET, MET status in CTCs correlated strongly with MET status in tumor tissue biopsies, illustrating the potential for using CTCs as a non-invasive, real-time biopsy to determine MET status of patients entering clinical trials. We are now expanding the CTC analysis on ISET to other biomarkers with relevance for lung therapeutics.
* Koeppen H et al. Clin Cancer Res. 2014 Sep 1;20(17):4488-98
Citation Format: Marius Ilie, Edith Szafer-Glusman, Veronique Hofman, Rebecca Suttman, Walter Darbonne, Charles-Hugo Marquette, David S. Shames, Elizabeth Punnoose, Paul Hofman. MET expression in circulating tumor cells (CTCs) isolated on the ISET platform correlates with MET expression in matched tumor tissue in advanced NSCLC patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1580. doi:10.1158/1538-7445.AM2015-1580