Abstract
BackgroundThe rate of diagnosis of advanced lung adenocarcinoma must be improved. In this study, we compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference.MethodsPaired blood and BWF specimens were collected from 73 patients with lung cancer. The tumor EGFR mutation status was determined by genotyping of the plasma and BWF samples using droplet digital PCR (ddPCR).ResultsThe study cohort included 26, 10, 10, and 27 patients with stage I, II, III, and IV disease. Of the 73 cases, 35 had a wild-type EGFR, and 19 had the L858R substitution and exon 19 deletion mutations. The areas under the receiver operator characteristic curves for sensitivity vs. specificity of ddPCR were 0.895 [95% confidence interval (CI): 0.822–0.969] for BWF and 0.686 (95% CI: 0.592–0.780) for plasma (p < 0.001). The fractional abundance was higher in BWF of the mEGFR-positive cases than in the plasma (p = 0.004), facilitating easy threshold setting and discrimination between mEGFR-positive and negative cases. When genotyping results obtained using plasma and BWF were compared for early lung cancer (stages I–IIIA), the diagnostic yields were significantly higher for BWF ddPCR, and the same tendency was observed for the advanced stages, suggesting that the BWF data may reflect the genotype status in early-stage patients.ConclusionsThe mEGFR genotyping results obtained using BWF showed a higher diagnostic efficacy than did those obtained using the plasma. Thus, BWF-based genotyping may be a useful substitute for that using plasma in lung cancer.
Highlights
IntroductionWe compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference
The rate of diagnosis of advanced lung adenocarcinoma must be improved
The ISEL-associated IPASS trial, which identified an EGFRactivating mutation [5], showed that the EGFR-the EGFRtyrosine kinase inhibitor (TKI) was more effective in patients with lung adenocarcinoma, who had EGFR-TKI-sensitizing mutations [6]
Summary
We compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference. The ISEL-associated IPASS trial, which identified an EGFRactivating mutation [5], showed that the EGFR-TKI was more effective in patients with lung adenocarcinoma, who had EGFR-TKI-sensitizing mutations (mEGFRs) [6]. Further phase III trials, which compared the outcomes of first- or second-line EGFR-TKI treatments with those of platinum doublets, confirmed the beneficial effects of mEGFRs on the progression-free survival and response rates in patients with lung adenocarcinoma [7]. It is important to identify target genes and accurately manage lung cancer, and mEGFRs are considered strong biomarkers for predicting the response to an EGFR-TKI
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