Correlation of epidermal growth factor receptor mutation status in plasma and tissue samples of patients with non-small cell lung cancer
Mee-Sook Roh1, Neul-Bom Yoon2, Seul Lee3, Bo-Hyoung Kang4, Soo-Jung Um4, Dong-Hyun Lee4, Choonhee Son4
1 Department of Pathology, College of Medicine, Dong-A University, Busan, South Korea
2 Department of Internal Medicine, Division of Pulmonology, Dongnam Institute of Radiological and Medical Sciences, Busan, South Korea
3 Department of Internal Medicine, Division of Pulmonology, Bong Seng Memorial Hospital, Busan, South Korea
4 Department of Internal Medicine, Division of Pulmonology, College of Medicine, Dong-A University, Busan, South Korea
Department of Internal Medicine, Division of Pulmonology, College of Medicine, Dong-A University, Daesingongwon-ro 26, Seo-gu, Busan 49201
Source of Support: None, Conflict of Interest: None
Background: Somatic mutations of the gene encoding epidermal growth factor receptor (EGFR) are detected in approximately 30%–50% of patients with non-small cell lung cancers (NSCLC), so detection of EGFR mutation is the pivotal step of treatment in patients with advanced NSCLC. However, difficulty in obtaining sufficient tissue and bias from the heterogeneity of the tumor samples are the major obstacles. Although analyzing EGFR with circulating tumor DNA (ctDNA) in plasma is a breakthrough, accuracy is the problem in variable methods. Peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve analysis (PANAMutyper®) is a novel and highly sensitive method of detecting EGFR mutation in tumor tissues.
Aims and Objectives: This study was designed to evaluate PANAMutyper® for detecting EGFR mutation with ctDNA of patients with lung cancer.
Materials and Methods: EGFR mutation status detected by PNA clamp with tissue samples and by PANAMutyper® with ctDNA was compared. Tissue biopsy was done in 158 patients with lung tumor, in which 23 cases were excluded and 135 cases were enrolled. EGFR mutation rate was 23.0% (31/135) in overall patients. All the plasma samples of the cases with mutant EGFR in tissue samples were verified by an already known highly sensitive method of droplet digital polymerase chain reaction (ddPCR).
Results: The concordance rate of tissue and plasma samples was 91.9% (124/135). The sensitivity, specificity, negative predictive value, and positive predictive value were 64.5%, 100%, 90.4%, and 100%, respectively, according to the tissue samples as a standard. PANAMutyper® method was not inferior to ddPCR for the detection of EGFR mutation including T790M with ctDNA. These results suggest that the detection of EGFR mutation status using ctDNA in plasma by PANAMutyper® is a feasible test prior to tissue biopsy.