Kobayashi Masashi, Sonobe Makoto, Takahashi Tsuyoshi, Yoshizawa Akihiko, Kikuchi Ryutaro, Date Hiroshi
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, and Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Asian Cardiovasc Thorac Ann. 2012 Aug;20(4):426-31. doi: 10.1177/0218492312440700.
To develop an easy-to-use technique for EML4-ALK detection and establish the effective selection of candidates for screening.
We previously reported clinicopathological findings of patients with lung cancer harboring the EML4-ALK fusion gene. Anaplastic lymphoma kinase inhibitors have therapeutic effects in lung cancer patients with EML4-ALK, accounting for merely 1%-5% of lung cancers.
We investigated EML4-ALK in tumors from 581 patients. EML4-ALK was detected by a reverse transcription polymerase-chain reaction and by the newly established criteria and algorithm using a fluorescence in situ hybridization method. To establish an algorithm to restrict candidates chosen for ALK fusion gene detection, clinicopathological findings as well as EGFR, ERBB2, and KRAS mutations were analyzed.
8 (1.3%) tumors had EML4-ALK, EGFR, KRAS, and ERBB2 mutations, which were mutually exclusive and were detected in 191 (32.8%), 56 (9.6%), and 11 (1.8%) tumors, respectively. We screened 581 patients with tumors and another 27 who were nonsmokers or mild smokers (<20 packs per year) lacking EGFR, KRAS, and ERBB2 mutations and who had adenocarcinomas exhibiting an acinar component with moderate or poor differentiation. Of the 27 patients, 8 (29.6%) had EML4-ALK.
We propose criteria for selecting candidates for efficient detection of the fusion gene.
开发一种易于使用的EML4-ALK检测技术，并建立有效的候选筛查选择方法。
我们之前报道了携带EML4-ALK融合基因的肺癌患者的临床病理特征。间变性淋巴瘤激酶抑制剂对携带EML4-ALK的肺癌患者具有治疗作用，此类患者仅占肺癌患者的1%-5%。
我们对581例患者的肿瘤进行了EML4-ALK检测。采用逆转录聚合酶链反应以及使用荧光原位杂交方法的新建立的标准和算法检测EML4-ALK。为建立一种限制选择进行ALK融合基因检测的候选者的算法，分析了临床病理特征以及EGFR、ERBB2和KRAS突变情况。
8例（1.3%）肿瘤存在EML4-ALK、EGFR、KRAS和ERBB2突变，这些突变相互排斥，分别在191例（32.8%）、56例（9.6%）和11例（1.8%）肿瘤中检测到。我们对581例肿瘤患者以及另外27例不吸烟或轻度吸烟（每年<20包）且缺乏EGFR、KRAS和ERBB2突变且腺癌呈腺泡状成分且分化中等或差的患者进行了筛查。在这27例患者中，8例（29.6%）存在EML4-ALK。
我们提出了有效检测融合基因的候选者选择标准。
