Correlation of epidermal growth factor receptor mutation status in plasma and tissue samples of patients with...

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.

This study was designed to evaluate PANAMutyper^® for detecting EGFR mutation with ctDNA of patients with lung cancer.

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).

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.