Suzuki Eriko, Sasaki Hidefumi, Kawano Osamu, Endo Katsuhiko, Haneda Hiroshi, Yukiue Haruhiro, Kobayashi Yoshihiro, Yano Motoki, Fujii Yoshitaka
Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.
Jpn J Clin Oncol. 2006 Jun;36(6):351-6. doi: 10.1093/jjco/hyl028. Epub 2006 Jun 8.
Epidermal growth factor receptor (EGFR) gene mutations have been reported to correlate with the sensitivity to the tyrosine kinase inhibitor treatment for advanced lung cancers. Since several reports have shown that invasive thymoma overexpress the EGFR protein, we examined the EGFR expression and mutation statuses in thymoma and thymic carcinoma tissues.
EGFR mutation statuses from 99 thymic epithelial tumor samples were evaluated by a rapid and sensitive TaqMan assay using Applied Biosysytems 7500 real-time PCR system. Probes were designed according to the 13 different EGFR mutations reported previously in lung cancers. A total of 38 thymoma samples were directly sequenced for the EGFR gene. Protein expressions were evaluated for 56 thymic epithelial tumors by immunohistochemistry.
EGFR gene mutations were not detected in any of the thymoma and thymic cancer samples using TaqMan PCR assay. Of the 38 samples 3 showed a heterozygous silent mutation without changes in the protein, a G to A transition at the nucleotide 2361 in exon 18. EGFR expression was significantly higher in invasive thymomas (stages III-IV, 15/19 were positive) than in early stage thymomas (stages I-II, 7/33 were positive) (P < 0.0001). All four carcinomas and all seven B3 thymomas showed EGFR positive staining.
Although EGFR mutation at the tyrosine kinase domain is unlikely to be a therapeutic target for thymoma, the information about EGFR expression would contribute to the further identification of the therapeutic target for advanced thymomas.
据报道，表皮生长因子受体（EGFR）基因突变与晚期肺癌对酪氨酸激酶抑制剂治疗的敏感性相关。由于有几份报告显示侵袭性胸腺瘤过度表达EGFR蛋白，我们检测了胸腺瘤和胸腺癌组织中EGFR的表达及突变状态。
使用Applied Biosysytems 7500实时PCR系统，通过快速灵敏的TaqMan检测法评估99例胸腺上皮肿瘤样本的EGFR突变状态。根据先前报道的肺癌中13种不同的EGFR突变设计探针。对38例胸腺瘤样本的EGFR基因进行直接测序。通过免疫组织化学评估56例胸腺上皮肿瘤的蛋白表达。
使用TaqMan PCR检测法在任何胸腺瘤和胸腺癌样本中均未检测到EGFR基因突变。在38个样本中，有3个显示杂合性沉默突变，蛋白无变化，即外显子18中核苷酸2361处由G到A的转变。侵袭性胸腺瘤（III-IV期，15/19为阳性）中的EGFR表达明显高于早期胸腺瘤（I-II期，7/33为阳性）（P < 0.0001）。所有4例癌和所有7例B3胸腺瘤均显示EGFR阳性染色。
尽管酪氨酸激酶结构域的EGFR突变不太可能成为胸腺瘤的治疗靶点，但有关EGFR表达的信息将有助于进一步确定晚期胸腺瘤的治疗靶点。
