Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma.
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.
Masago
Katsuhiro
K
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Asato
Ryo
R
Fujita
Shiro
S
Hirano
Shigeru
S
Tamura
Yoshihiro
Y
Kanda
Tomoko
T
Mio
Tadashi
T
Katakami
Nobuyuki
N
Mishima
Michiaki
M
Ito
Juichi
J
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*
D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf