Next generation sequencing-based molecular profiling of lung adenocarcinoma using pleural effusion specimens

J Thorac Dis. 2018 May;10(5):2631-2637. doi: 10.21037/jtd.2018.04.125.


Background: Molecular profiling of non-small cell lung cancer (NSCLC) is essential for therapeutic decision-making. Pleural effusion obtained by a non-invasive, repeatable procedure may provide an opportunity for molecular profiling and thereby possibly provide information enabling targeted therapy. In this study, we aimed to evaluate the diagnostic performance of pleural effusion as a specimen for molecular analysis.

Methods: Thirty patients with paired malignant pleural effusion and thoracic biopsy specimens were included. Clinically actionable mutations were assessed using a validated targeted next generation sequencing assay. EGFR/KRAS/ALK mutation status in thoracic biopsy specimens was tested using ARMS PCR.

Results: The concordance rate between gene status identified by ARMS and next-generation sequencing (NGS) analysis in the thoracic biopsy and pleural effusion samples was 86.7% (26/30). Compared with the thoracic biopsy specimens, the diagnostic performance of pleural effusion showed a sensitivity of 92.3%, a specificity of 50.0%, and a positive predictive value of 92.3%. Therefore, cases with a low percentage of tumor cells (<5%) can successfully be used to detect actionable mutations in pleural effusion specimens.

Conclusions: These results suggest that pleural effusions are suitable specimens for oncogene mutation analysis and enable targeted therapy for patients with advanced NSCLC.

Keywords: Pleural effusion; actionable genomic alteration; lung adenocarcinoma; next generation sequencing.