Utility of liquid biopsy for EGFR mutation testing in lung adenocarcinoma in a resource-limited setting

Abstract

EGFR mutation testing is key for the management of lung adenocarcinoma. Here, we aimed to examine the contribution of liquid biopsy versus tissue biopsy and formalin-fixed paraffin-embedded (FFPE) tissue to EGF R mutation testing in lung adenocarcinoma in a resource-limited setting. This study included 54 patients with confirmed lung adenocarcinoma, 31 patients from a retrospective cohort and 23 from a prospective cohort. The Therascreen EGFR RGQ PCR Kit (Qiagen) was used for the identification of EGFR mutations from DNA samples extracted from tissue biopsy or FFPE tissue. A Therascreen EGFR plasma RGQ PCR Kit (Qiagen) was used for the detection of EGFR mutations from DNA samples extracted from liquid biopsy. The DNA extracted from the FFPE tissues was significantly degraded, whereas the DNA extracted from the tissue biopsies or liquid biopsies was of good quality. EGFR mutations were detected in circulating tumor DNA (ctDNA) samples extracted from liquid biopsies in 17.4% of the patients in the prospective cohort. Moreover, a dual mutation (exon 19 deletion and the T790M resistance mutation conferring resistance to first- and second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs)) was detected among the positive cases. However, no EGFR mutations were detected in the DNA samples extracted from tissue biopsies from all patients, notably even in cases where EGFR mutations had been detected in ctDNA samples, suggesting that in these cases, the tissue biopsies collected for molecular analysis did not contain cancerous tissue. Conclusions : To our knowledge, this is the first study conducted in Morocco on EGFR testing in lung adenocarcinoma using ctDNA. Our results clearly demonstrated the utility of liquid biopsy versus tissue biopsy for EGFR mutation testing, especially when DNA extracted from FFPE tissues is degraded or in cases of limited tissue material. Our findings also showed that liquid biopsy can overcome spatial tumor heterogeneity by identifying multiple mutations. Therefore, this study supports the clinical integration of this noninvasive method for assessing tumor characteristics and monitoring disease progression when obtaining a tissue biopsy is challenging.