Molecular testing of different cytologic preparations in patients with advanced lung adenocarcinoma: which yields the best results?

Abstract

This study constitutes the first systematic comparison of molecular results between different cytology preparations in patients with lung adenocarcinoma undergoing testing for EGFR, KRAS, and BRAF mutations. 115 archival cytology preparations (direct smears, ThinPrep preparations [TP], and cell blocks [CB]) from lung adenocarcinomas with known EGFR, KRAS, or BRAF mutations were tested and compared with clinical testing results. Results were compared between preparations and analyzed in relation to tumor purity and tumor cell content. 82 (77%) of 106 informative cases were concordant with clinical testing results. There was no significant difference in the concordance rate between CB, TP, air-dried smears, or alcohol-fixed smears (P=0.3803), nor between preparations with <25%, 25% to 50%, or >50% tumor purity (P=0.1147). Concordance rates were lower in preparations with ≤100 tumor cells (P = 0.0002). Smears, TP, and CB are all valid substrates for molecular testing. Although tumor purity did not significantly affect results, low tumor content showed poorer performance. Recording tumor purity and content is recommended.