Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.
J Thorac Oncol. 2012 Jan;7(1):98-104. doi: 10.1097/JTO.0b013e3182370e30.
The echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion represents a novel target in a subset of non-small cell lung cancer, especially adenocarcinoma. EML4-ALK fusion is mutually exclusive with epidermal growth factor receptor (EGFR) mutations. To understand the impact of EML4-ALK on the prognosis of non-small cell lung cancer, we examined EML4-ALK fusion in lung adenocarcinoma from patients with wild-type EGFR and analyzed their clinical treatment outcomes.
Lung adenocarcinoma patients with malignant pleural effusions having wild-type EGFR and measurable target lesions were enrolled for EML4-ALK analysis by reverse transcription-polymerase chain reaction and direct sequencing. Demographic data, EML4-ALK status, and survival data were analyzed. We also performed fluorescence in situ hybridization on some available tumor samples to validate the PCR result. In addition, K-ras mutation was analyzed for patients without EML4-ALK fusion genes.
A total of 116 patients with wild-type EGFR sequencing results had complete clinical data for analysis. No patients received ALK inhibitor therapy. There were 39 patients (34%) with the EML4-ALK fusion gene. The concordance rate between reverse transcription-polymerase chain reaction and fluorescence in situ hybridization was 85%. The K-ras mutation rate for patients without EML4-ALK fusion gene was 6.5%. By multivariate analysis, patients who had better performance status (p < 0.001) and EML4-ALK translocation (p = 0.017) had longer overall survival. Comparing patients with tumors harboring variant 1 with those harboring nonvariant 1 EML4-ALK fusion genes, there were no significant differences in clinical factors and survival outcome.
For lung adenocarcinoma patients with wild-type EGFR, EML4-ALK translocation is associated with longer overall survival.
棘皮动物微管相关蛋白样 4-间变性淋巴瘤激酶（EML4-ALK）融合是一种新型的非小细胞肺癌治疗靶点，尤其在腺癌中。EML4-ALK 融合与表皮生长因子受体（EGFR）突变相互排斥。为了了解 EML4-ALK 对非小细胞肺癌预后的影响，我们检测了野生型 EGFR 的肺腺癌中 EML4-ALK 融合，并分析了它们的临床治疗结果。
纳入具有野生型 EGFR 和可测量靶病灶的恶性胸腔积液肺腺癌患者，通过逆转录-聚合酶链反应和直接测序分析 EML4-ALK 融合。分析患者的人口统计学数据、EML4-ALK 状态和生存数据。我们还对部分可用肿瘤样本进行了荧光原位杂交以验证 PCR 结果。此外，对于没有 EML4-ALK 融合基因的患者，我们还分析了 K-ras 突变。
共 116 例具有完整野生型 EGFR 测序结果的患者纳入分析。没有患者接受过 ALK 抑制剂治疗。39 例（34%）患者存在 EML4-ALK 融合基因。逆转录-聚合酶链反应与荧光原位杂交的一致性率为 85%。无 EML4-ALK 融合基因的患者 K-ras 突变率为 6.5%。多因素分析显示，功能状态较好的患者（p<0.001）和存在 EML4-ALK 易位的患者（p=0.017）总体生存时间更长。比较存在变异 1 型肿瘤和存在非变异 1 型 EML4-ALK 融合基因的肿瘤患者，在临床因素和生存结果方面无显著差异。
对于野生型 EGFR 的肺腺癌患者，EML4-ALK 易位与更长的总体生存时间相关。
