Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Oncology. 2012;83(5):248-56. doi: 10.1159/000341381. Epub 2012 Sep 4.
To identify the clinicopathological characteristics and clinical outcomes of Chinese patients with non-small cell lung cancer (NSCLC) and to investigate possible associations of NSCLC with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutations.
Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at the Peking University Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization and confirmed by immunohistochemistry. EGFR mutations were determined using denaturing high-performance liquid chromatography.
The incidence of EML4-ALK was 9.7% (11/113). Patients with EML4-ALK were more likely to present the EGFR wild type (WT; p = 0.033). Response to EGFR-tyrosine kinase inhibitor (TKI) was similar between patients with EML4-ALK rearrangement and EGFR mutation (33.3 vs. 46.9%, p = 0.451), but progression-free survival (PFS) was inferior compared to those with EGFR mutation (2.1 vs. 8.8 months, p = 0.032), and similar to patients with WT/nonrearrangement (2.1 vs. 2.2 months, p = 0.696; and general p = 0.023 between the three cohorts). Moreover, 2 patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared to patients with single EML4-ALK rearrangement.
Patients with EML4-ALK conferred similar objective response rates after EGFR-TKI although inferior PFS compared to those with EGFR mutation. Coexistence of EML4-ALK and EGFR mutation might represent a separate NSCLC genotype.
鉴定中国非小细胞肺癌（NSCLC）患者的临床病理特征和临床结局，并研究 NSCLC 与棘皮动物微管相关蛋白样 4（EML4）-间变性淋巴瘤激酶（ALK）和表皮生长因子受体（EGFR）突变的可能关联。
在北京大学肿瘤医院对 IV 期 NSCLC 患者进行 EML4-ALK 重排和 EGFR 突变筛查。使用荧光原位杂交法鉴定 EML4-ALK，并通过免疫组织化学法进行确认。采用变性高效液相色谱法确定 EGFR 突变。
EML4-ALK 的发生率为 9.7%（11/113）。EML4-ALK 患者更可能表现为 EGFR 野生型（WT；p = 0.033）。EML4-ALK 重排患者与 EGFR 突变患者对 EGFR-酪氨酸激酶抑制剂（TKI）的反应相似（33.3%比 46.9%，p = 0.451），但无进展生存期（PFS）不如 EGFR 突变患者（2.1 比 8.8 个月，p = 0.032），与 WT/非重排患者相似（2.1 比 2.2 个月，p = 0.696；总体 p = 0.023）。此外，2 例同时存在 EML4-ALK 和 EGFR 突变的患者在接受 EGFR-TKI 治疗后 PFS 优于仅存在 EML4-ALK 重排的患者。
与 EGFR 突变患者相比，EML4-ALK 患者接受 EGFR-TKI 治疗后客观缓解率相似，但 PFS 较差。EML4-ALK 和 EGFR 突变的共存可能代表一种独立的 NSCLC 基因型。
