Sputum Cell-free DNA: Valued Surrogate Sample for Detection of EGFR Mutation in Patients with Advanced Lung Adenocarcinoma

Sputum is common cytological sample type, but its potential use in EGFR mutation detection in patients with lung cancer is not fully evaluated. An improved sputum cfDNA extraction method was established in this study, and applied super-amplification refractory mutation system (SuperARMS) to detect the EGFR mutation status in sputum cfDNA. The sputum sediments were used for cytology evaluation. The study included 102 lung adenocarcinoma patients, in which 65 (63.7%) patients were positive for EGFR mutations in tumor samples. EGFR mutation status was shown to be positive in 30 (29.4%) patients by sputum cfDNA testing, achieving an overall sensitivity and specificity of 46.2% and 100%, respectively. Comparison of EGFR mutation status in tumor samples revealed that the sensitivity of testing sputum cfDNA in 40 patients with stage I-IIIA versus 62 patients with stage IIIB-IV was 24% (6/25) versus 65.0% (26/40). Through cytology evaluation, the sputum specimens from 62 advanced patients were classified into three categories: 10 were in unsatisfactory; 34 were in satisfactory but no malignant cells; and 18 were in malignant. The sensitivities of these three categories were 0% (0/8), 71.4% (15/21), 100% (11/11), respectively. These findings revealed that with the improved cfDNA extraction method and sputum cytology evaluation, sputum cfDNA is considered to be a valuable surrogate sample type for detecting clinical EGFR mutations in advanced lung adenocarcinoma patients.