Masago Katsuhiro, Asato Ryo, Fujita Shiro, Hirano Shigeru, Tamura Yoshihiro, Kanda Tomoko, Mio Tadashi, Katakami Nobuyuki, Mishima Michiaki, Ito Juichi
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Int J Cancer. 2009 Jun 1;124(11):2744-9. 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.
近期研究表明，在一部分非小细胞肺癌（NSCLC）患者中已鉴定出表皮生长因子受体（EGFR）基因的体细胞突变，且这些突变与对EGFR酪氨酸激酶抑制剂的敏感性相关。据报道，这些突变几乎仅在NSCLC的肺腺癌亚组中发现，在其他实体瘤中的发生率较低。我们描述了一名晚期乳头状甲状腺癌（PTC）患者，其疾病最初被诊断为肺腺癌，并且对EGFR酪氨酸激酶抑制剂吉非替尼有显著反应。在该患者的肿瘤标本中发现了外显子19的框内缺失，该缺失消除了746至750位的4个氨基酸，这是肺腺癌中常见的药物敏感突变之一，以及密码子752处的丝氨酸到脯氨酸替代。我们随后在23例PTC患者的原发性肿瘤中搜索EGFR酪氨酸激酶结构域的突变，其中7例患者发现了肺腺癌中常见的药物敏感突变。我们观察到PTC中EGFR激活突变的高频率表明，EGFR突变可能是PTC发生发展中的一个重要事件。EGFR基因扩增也被认为是对EGFR酪氨酸激酶抑制剂反应的预测指标，通过荧光原位杂交（FISH）进行评估；然而，仅检测到1例FISH阳性肿瘤。我们的数据表明，EGFR酪氨酸激酶抑制剂可能值得考虑用于治疗一部分PTC患者，就像治疗肺腺癌一样。
