title: Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma.
abstract: Recent studies have indicated that somatic mutations in the epidermal growth factor receptor (EGFR) gene have been identified in a subset of patients with nonsmall-cell lung cancer (NSCLC) and are associated with sensitivity to the EGFR-tyrosine-kinase inhibitors. These mutations have been reported to be almost exclusively found in a pulmonary adenocarcinoma subgroup of NSCLC, with a low frequency in other solid tumors. We describe a patient with advanced-stage papillary thyroid carcinoma (PTC) whose disease had been diagnosed as pulmonary adenocarcinoma at first, and who had a marked response to the EGFR-tyrosine-kinase inhibitor, gefitinib. An in-frame deletion in exon 19 that eliminated 4 amino acids at positions 746 through 750, which is one of the common drug-sensitive mutations in pulmonary adenocarcinoma, and a serine-to-proline substitution at codon 752, were found in a tumor specimen of the patient. We subsequently searched for mutations in the EGFR tyrosine kinase domain in primary tumors from 23 patients with PTC, and drug-sensitive mutations commonly observed in pulmonary adenocarcinoma were found in 7 of these patients. Our observation of a high frequency of the EGFR-activating mutations in PTC suggests that the EGFR mutation may be an important event in the development of PTC. EGFR gene amplification, also considered to be a predictor of response to EGFR-tyrosine-kinase inhibitors, was evaluated by fluorescence in situ hybridization (FISH); however, only 1 FISH-positive tumor was detected. Our data suggest that EGFR-tyrosine-kinase inhibitors may deserve consideration in the treatment of a subset of patients with PTC, just as with pulmonary adenocarcinoma.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Masago
authors.forename: Ryo
authors.initials: R
authors.lastname: Asato
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hirano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tamura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kanda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Mio
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
mesh_terms: D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf