Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling

Background The clinical utility of malignant pleural effusion (MPE) to detect mutation has been well documented; however, routine practice of the use of MPE involves collection of the cell pellet to detect mutation, and limited studies have interrogated the MPE supernatant as an alternative source of tumor‐derived DNA for mutation profiling. In this study, we investigated the potential of MPE supernatant as a liquid biopsy specimen by comparing its mutation profile with that of matched MPE cell pellets, tissue, and plasma samples. Methods Sequencing data from 17 patients with matched lung tissue, plasma, and MPE samples were retrospectively analyzed. Capture‐based targeted sequencing was performed on matched plasma and MPE supernatant samples obtained from 154 patients with advanced lung adenocarcinoma. Results MPE supernatants had significantly higher median maximum allelic fractions (maxAFs) than their corresponding cell pellets (P = 0.008) and plasma samples (P = 0.036), and a comparable maxAF value to that of tissue samples (P = 0.675). Comparison of MPE supernatant and matched plasma samples from the larger cohort (n = 154) revealed a comparable mutation detection rate; however, MPE supernatant had a significantly higher median maxAF than plasma (20.3% vs. 1.13%; P