Matsumoto Shingo, Takahashi Kenji, Iwakawa Reika, Matsuno Yoshihiro, Nakanishi Yukihiro, Kohno Takashi, Shimizu Eiji, Yokota Jun
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Int J Cancer. 2006 Sep 15;119(6):1491-4. doi: 10.1002/ijc.21940.
Lung adenocarcinomas often metastasize to the brain, and the prognosis of patients with brain metastases is still very poor. The epidermal growth factor receptor (EGFR) gene is mutated in a considerable fraction of primary lung adenocarcinomas, in particular those with drastic response to EGFR tyrosine kinase inhibitors. The present study was designed to elucidate the prevalence of EGFR mutations in brain metastases and the timing of their occurrence during cancer progression. EGFR mutations were detected in 12 of 19 metastatic lung adenocarcinomas to the brain (63%). This frequency was higher than those in previous studies for EGFR mutations at various stages of lung adenocarcinoma in East Asia, including Japan (i.e., 20-55%). In 6 cases with EGFR mutations, the corresponding primary lung tumors were also examined for the mutations, and in all of them, the same types of EGFR mutations were detected also in the primary tumors. In 2 of them, second metastatic brain tumors in addition to the first ones were also available for analysis, and the same types of EGFR mutations were detected in both the first and second ones in both cases. These results indicate that EGFR mutations are present frequently in brain metastases and occur preceding brain metastasis. These findings will be highly informative for treatment of metastatic lung adenocarcinoma to the brain.
肺腺癌常发生脑转移，脑转移患者的预后仍然很差。表皮生长因子受体（EGFR）基因在相当一部分原发性肺腺癌中发生突变，尤其是那些对EGFR酪氨酸激酶抑制剂有显著反应的腺癌。本研究旨在阐明EGFR突变在脑转移瘤中的发生率及其在癌症进展过程中的发生时间。在19例脑转移肺腺癌中，有12例检测到EGFR突变（63%）。这一频率高于此前东亚地区包括日本在内的关于肺腺癌各阶段EGFR突变的研究（即20%-55%）。在6例有EGFR突变的病例中，也对相应的原发性肺肿瘤进行了突变检测，所有病例的原发性肿瘤中均检测到相同类型的EGFR突变。其中2例除了首个脑转移瘤外还有第二个脑转移瘤可供分析，两例的首个和第二个脑转移瘤均检测到相同类型的EGFR突变。这些结果表明，EGFR突变在脑转移瘤中频繁出现，且在脑转移之前就已发生。这些发现对于脑转移肺腺癌的治疗具有重要意义。
