Analysis of EGFR mutation status in malignant pleural effusion and plasma from patients with advanced lung adenocarcinoma.

Background Cell-free DNA (cfDNA) is emerging as a surrogate sample type for mutation analyses. We investigated the suitability of malignant pleural effusion (MPE) and plasma as a biomaterial for analyzing epidermal growth factor receptor (EGFR) mutation by peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve (PANAMutyper) analysis. Methods Matched tissue, MPE cell block (MPE-CB), MPE supernatant, and plasma samples were collected from patients with advanced lung adenocarcinoma who had a MPE at the time of diagnosis. EGFR mutation was assessed by PANAMutyper. Results Mutation analyses in matched tumor tissues, MPE-CB, MPE supernatant, and/or plasma samples were available for 67 patients. In comparison with tumor tissue and MPE-CB, MPE supernatant exhibited 84.4% sensitivity, 97.1% specificity, 96.4% positive predictive value (PPV), and 87.2% negative predictive value (NPV). In the same comparison, plasma exhibited 70.6% sensitivity, 100.0% specificity, 100.0% PPV, and 73.7% NPV. When sorted by mutation type, MPE supernatant had better sensitivity than plasma for the detection of two major EGFR mutations: 93.8% vs. 75.0% for exon 19 deletion and 73.3% vs. 60.0% for L858R. Conclusions In this cohort of patients with MPEs, MPE supernatant demonstrated superior diagnostic performance compared with plasma using a PNA-based real-time PCR method.