Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma

• Published in: International journal of cancer Vol. 124; no. 11; pp. 2744 - 2749
• Main Authors: Masago, Katsuhiro, Asato, Ryo, Fujita, Shiro, Hirano, Shigeru, Tamura, Yoshihiro, Kanda, Tomoko, Mio, Tadashi, Katakami, Nobuyuki, Mishima, Michiaki, Ito, Juichi
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2009; Wiley-Blackwell
• Subjects: Adult; Aged; Biological and medical sciences; Carcinoma, Papillary - drug therapy; Carcinoma, Papillary - genetics; EGFR; Endocrinopathies; Female; Humans; Male; Malignant tumors; Medical sciences; molecular‐targeted therapy; Mutation; Proto-Oncogene Proteins B-raf - genetics; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; thyroid carcinoma; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - genetics; Thyroid. Thyroid axis (diseases); Tumors; Endocrinopathy; Antineoplastic agent; Targeted therapy; Quinazoline derivatives; Epidermal growth factor receptor; EGFR; thyroid carcinoma; Cancerology; Gene; Genetics; Adult; Female; Gefitinib; Protein-tyrosine kinase; Human; Enzyme; Tyrosine kinase inhibitor; molecular-targeted therapy; Transferases; Thyroid diseases; Enzyme inhibitor; Malignant tumor; Case study; Chemotherapy; Treatment; Thyroid cancer; Mutation; Papillary thyroid carcinoma; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.24250

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. © 2008 Wiley‐Liss, Inc.