Liquid biopsy in patients with adenocarcinoma -comparison between bronchoalveolar lavage (BAL) and blood samples

Abstract

Background: Formalin-Fixed Paraffin-Embedded Tissue (FFPET) samples remain the golden standard for EGFR genotyping. In many cases the initial sample is insufficient. EGFR genotyping could be done on BAL or blood samples. In the last few years, liquid biopsies prove to be a reliable method for EGFR characterization, but the cytology samples are not used very often. In this study, we compare the detection rate of EGFR mutations in BAL and blood samples compared to FFPET samples.

Material and Method: For 12 months, bronchoscopy was performed on 140 patients suspected of lung cancer. Forceps biopsy, BAL and blood samples were obtained in all of them. The DNA extraction was performed with QIAAmp Circulating Nucleic Acid kit for plasma and BAL samples. Activating mutations were confirmed based on EGFR genotyping in FFPET samples.

Results: Adenocarcinoma was present in 26 of the patients with lung cancer which were verified with immunohistochemistry. Adenocarcinoma with EGFR activating mutations on FFPET was present in 13 cases. 8 patients had deletions in exon 19, 4 had L858R substitution in exon 21 and one patient had G719x in exon 18. In 12 cases mutations were confirmed in corresponding BAL samples (92.3%) and they were detected in only 5 plasma samples (38.5%). In 1 case in both BAL and plasma liquid biopsy samples we found T790M mutation along with deletion in exon 19, but not in the corresponding FFPET sample which yielded only exon 19 deletion.

Conclusion: This study shows that BAL samples are superior to plasma samples and almost equal to FFPET samples in detecting EGFR mutations, therefore BAL samples should be preferred before blood samples when possible.