title: EGFR mutation status in pleural fluid predicts tumor responsiveness and resistance to gefitinib.
abstract: It has been reported that the threonine-to-methionine substitution at amino acid position 790 (T790M) of the epidermal growth factor receptor (EGFR) gene is correlated with acquired resistance to gefitinib. We previously reported that there was some population that harbored the EGFR T790M mutation as a minor clone of tumor cells prior to drug treatment, may be causing resistance to gefitinib during treatment. This fact also suggests that the detection of the EGFR T790M mutation prior to treatment may predict the development of resistance. We also showed that pleural fluid is a useful specimen for detection of EGFR mutation using sensitive assays. In this study, we reported a female patient who was treated with gefitinib because an EGFR L858R mutation was found in her pleural fluid. Our patient showed partial response to gefitinib, but she had progressive disease only 4 months after the start of treatment. Furthermore, the EGFR T790M mutation was detected in the pleural fluid before gefitinib treatment by the mutant-enriched PCR assay. Our findings confirmed that the EGFR T790M mutation was occasionally present as a minor population in tumor cells before treatment and caused resistance after gefitinib administration. The detection of a small fraction of T790M-positive alleles may be useful to predict the clinical course of the gefitinib-treated non-small-cell lung cancer patients.
authors.affiliation: Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Shuji
authors.initials: S
authors.lastname: Ichihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suehisa
authors.forename: Naruyuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Sachio
authors.initials: S
authors.lastname: Ito
authors.forename: Masaomi
authors.initials: M
authors.lastname: Yamane
authors.forename: Motoi
authors.initials: M
authors.lastname: Aoe
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sano
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D009154:Mutation; D016066:Pleural Effusion, Malignant / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib