title: Usefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancer.
abstract: The importance of epidermal growth factor receptor (EGFR) gene mutation has been recognized in nonsmall cell lung cancer (NSCLC), requiring the standardization of mutation screening system including the kind of samples. Here, we examined the EGFR mutation status in 61 pleural fluid samples from NSCLC cases using direct sequencing, nonenriched PCR, mutant-enriched PCR and peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp assay. The mutant-enriched PCR assay detected 16 mutant cases. Among them, the nonenriched PCR assay failed to detect 3 mutant cases. Regarding the discrepancy between mutant-enriched PCR and PNA-LNA PCR clamp assays, 3 cases of exon19-deletions were detected only by mutant-enriched PCR assay and no difference at the L858R mutation. There was no difference in results between direct sequencing and nonenriched PCR assay. We also correlated the EGFR mutation with clinical outcome of gefitinib-treated 29 cases. EGFR mutations were present in 10 cases, revealing 7 partial response and 3 no change (NC). In EGFR wild-type cases, 10 revealed NC and 9 progressive disease. The responders were significantly more frequent among the EGFR mutant cases than among the wild-type (p < 0.0001). Overall survival (p = 0.0092) and progression-free survival (p = 0.018) were significantly longer among the EGFR mutant cases than among the wild-type. In summary, we evaluated the utility of EGFR mutation screening in pleural fluid using 4 assays that showed some discrepancies arising from the designs of the assays. As clinical importance, the EGFR mutation status in pleural fluid can be a biomarker for the favorable outcome of gefitinib-treated NSCLC cases.
authors.affiliation: Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aoe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Asano
authors.forename: Syuji
authors.initials: S
authors.lastname: Ichihara
authors.forename: Hideki
authors.initials: H
authors.lastname: Katayama
authors.forename: Akio
authors.initials: A
authors.lastname: Hiraki
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Motoi
authors.initials: M
authors.lastname: Aoe
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sano
authors.forename: Kazuro
authors.initials: K
authors.lastname: Sugi
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D005820:Genetic Testing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation; D016066:Pleural Effusion, Malignant / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib