Tseng, Jeng-SenJeng-SenTsengWang, Chih-LiangChih-LiangWangHuang, Ming-ShyanMing-ShyanHuangCHUNG-YU CHENChang, Cheng-YuCheng-YuChangYang, Tsung-YingTsung-YingYangTsai, Chi-RenChi-RenTsaiChen, Kun-ChiehKun-ChiehChenHsu, Kuo-HsuanKuo-HsuanHsuTsai, Meen-HsinMeen-HsinTsaiSUNG-LIANG YUKANG-YI SUWu, Chih-WeiChih-WeiWuYang, Cheng-TaCheng-TaYangChen, Yuh-MinYuh-MinChenMONG-HSUN TSAI2021-08-232021-08-2320141932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-84926038463&doi=10.1371%2fjournal.pone.0107160&partnerID=40&md5=fd848fbd5cda72e0a052a240b7e8ee3fhttps://scholars.lib.ntu.edu.tw/handle/123456789/579191Introduction: Methods used for epidermal growth factor receptor (EGFR) mutation testing vary widely. The impact of detection methods on the rates of response to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-wild type (wt) lung adenocarcinoma patients is unknown. Methods: We recruited the Group-I patients to evaluate the efficacy of erlotinib in patients with EGFR-wt lung adenocarcinoma by either direct sequencing (DS) or mutant type-specific sensitive (MtS) methods in six medical centers in Taiwan. Cross recheck of EGFR mutations was performed in patients who achieved objective response to erlotinib and had adequate specimens. The independent Group-II lung adenocarcinoma patients whose EGFR mutation status determined by DS were recruited to evaluate the potential limitations of three MtS methods. Results: In Group-I analysis, 38 of 261 EGFR-wt patients (14.6%) achieved partial response to erlotinib treatment. Nineteen patients (50.0%) had adequate specimens for cross recheck of EGFR mutations and 10 of them (52.6%) had changes in EGFR mutation status, 5 in 10 by DS and 5 in 9 by MtS methods originally. In Group-II analysis, 598 of 996 lung adenocarcinoma patients (60.0%) had detectable EGFR mutations. The accuracy rates of the three MtS methods, MALDI-TOF MS, Scorpions ARMS and Cobas, were 87.8%, 86.8% and 85.8%, respectively. Conclusions: A significant portion of the erlotinib responses in EGFR-wt lung adenocarcinoma patients were related to the limitations of detection methods, not only DS but also MtS methods with similar percentages. Prospective studies are needed to define the proper strategy for EGFR mutation testing. ? 2014 Tseng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.[SDGs]SDG3epidermal growth factor receptor; erlotinib; epidermal growth factor receptor; erlotinib; quinazoline derivative; adult; aged; amplification refractory mutation system; Article; controlled study; direct sequencing; drug efficacy; drug fatality; drug response; EGFR gene; female; gene amplification; gene mutation; human; intermethod comparison; interstitial lung disease; liver toxicity; lung adenocarcinoma; major clinical study; male; matrix assisted laser desorption ionization time of flight mass spectrometry; measurement accuracy; middle aged; mutational analysis; polymerase chain reaction; polymerase chain reaction system; sequence analysis; Taiwan; very elderly; wild type; adenocarcinoma; cancer staging; cohort analysis; genetics; Kaplan Meier method; Lung Neoplasms; mutation; nucleotide sequence; pathology; procedures; treatment outcome; Adenocarcinoma; Aged; Cohort Studies; DNA Mutational Analysis; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasm Staging; Quinazolines; Receptor, Epidermal Growth Factor; Treatment Outcomejournal article10.1371/journal.pone.0107160252155362-s2.0-84926038463