Abstract
BACKGROUND: There are no prospective studies to estimate whether cytology specimens can replace tissue samples using lung cancer gene panel analysis. We evaluated the success rate of gene panel testing and nucleic acid yield and quality when using cytology specimens for lung cancer over tissue specimens. METHODS: In this prospective study, clinical cytology specimens collected via transbronchial brushing, needle aspiration washing, and pleural effusion were stored in a nucleic acid stabilizer. The primary endpoint was the superior success rate of gene analysis using cytology specimens over the conventional success rate using tissue specimens. RESULTS: The full analysis set included 248 cases. The success rate for gene panel analysis using cytology specimens was 98.4% (95% confidence interval (CI), 95.9-99.6%) with a positive concordance rate of 97.3% (95% CI, 90.7-99.7%) by other companion diagnostic kits. The median value for nucleic acid yield and quality (DNA/RNA integrated number) of cytology specimens was 546.0/426.5 ng and 9.2/4.7 for DNA/RNA, respectively. The Pearson correlation coefficient of variant allele frequency between tissue formalin-fixed and paraffin-embedded (FFPE) sample and cytology specimens for mutant cases was 0.815. The ratio of double-stranded to total DNA showed that cytology specimens were of significantly higher quality than FFPE specimens. CONCLUSIONS: The success rate of cytology specimens in gene analysis was significantly higher than conventional data. Because of the sufficient nucleic acid yield, high quality, and high correlation of mutant allele frequency compared to FFPE specimens, cytology specimens are suitable for panel testing as tissue substitutes. TRIAL REGISTRATION: UMIN Registry UMIN000047215 (cPANEL trial). https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053766 .