title: A rapid, sensitive assay to detect EGFR mutation in small biopsy specimens from lung cancer.
abstract: It has been demonstrated that lung cancers, specifically a subset of pulmonary adenocarcinomas, with epidermal growth factor receptor (EGFR) mutation are highly sensitive to EGFR-targeted drugs. Therefore, a rapid, sensitive assay for mutation detection using routine pathological specimens is demanded in clinical practice to predict the response. We therefore developed a new assay for detecting EGFR mutation using only a paraffin section of a small biopsy specimen. The method was very sensitive, detecting as few as 5% cancer cells in a background of normal cells, the results usually being obtained within 4 hours. Furthermore, it was accurate, as shown by the high concordance with reverse transcriptase-polymerase chain reaction-coupled direct sequencing (186 of 195, 95%). The practical application of this assay to 29 cases treated with gefitinib resulted in a high prediction rate: 10 of the 11 responders were shown to be positive for the mutation, and all patients with progressive disease were negative. In addition, a mutation at codon 790, conferring gefitinib resistance, was successfully analyzed in a similar manner. In conclusion, the assay is a rapid, sensitive method using paraffin sections of biopsy specimens without a tumor cell-enrichment procedure and is quite useful to select a treatment of choice in clinical practice.
authors.affiliation: Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Kanokoden, Nagoya 464-8681, Japan. yyatabe@aichi-cc.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Horio
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kosaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
mesh_terms: D001706:Biopsy / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008875:Middle Aged; D008954:Models, Biological; D017354:Point Mutation; D011237:Predictive Value of Tests; D011799:Quinazolines / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D017211:Treatment Failure
chemical_list: D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib