Detection of EGFR Mutation of Pulmonary Adenocarcinoma in Sputum Using Droplet Digital PCR

Background: It is still unclear whether epidermal growth factor receptor (EGFR) mutation of primary lung adenocarcinoma can be detected accurately on sputum samples. This study aimed to examine EGFR mutations of primary lung adenocarcinoma in sputum samples using droplet digital polymerase chain reaction (ddPCR) and compare it with an EGFR mutation in surgically resected lung cancer. Methods: Sputum was collected preoperatively from patients with primary lung cancer who were scheduled for complete resection of lung tumor at Kanagawa Cancer Center from September 2014 to May 2016. ddPCR was performed to detect EGFR exon 21 L858R point mutation (Ex21 mutation) and EGFR exon 19 deletion mutation (Ex19 mutation) in the sputum samples. The concordance of EGFR mutation status in sputum samples and tumors in surgically resected specimen was evaluated for each positive and negative cytology group. Results: One hundred and eighteen patients with primary lung adenocarcinoma provided sputum samples. Sputum cytology was positive in 13 patients (11.0%). ddPCR detected two cases of Ex21 mutation and two cases of Ex19 mutation. Compared to surgically resected specimens, the sensitivity, specificity, and positive predictive value of EGFR mutation detection were 80.0%, 100%, and 92.3%, respectively. The sensitivity of EGFR mutation detection was 3.1% in sputum cytology negative cases. Logistic regression model analysis revealed that tumor size ≥ 29 mm determined using computed tomography (CT) was an independent potential predictive factor for positive sputum cytology (odds ratio = 10.6, 95% confidence interval: 1.85–61.0, p=0.008). Conclusions: EGFR mutation of primary lung adenocarcinoma was accurately detected in sputum samples using ddPCR if the sputum cytology was positive. Sputum samples should be collected in patients with CT tumor size ≥ 29 mm for EGFR mutation analysis.