Tao Hong, Shi Liang, Zhou Aoxue, Li Hongxia, Gai Fei, Huang Zhan, Che Nanying, Liu Zhe
Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Amoy Diagnostics Co., Ltd, Xiamen, China.
Lung Cancer. 2020 Nov;149:154-161. doi: 10.1016/j.lungcan.2020.09.012. Epub 2020 Sep 24.
The molecular profiles and prognosis of anaplastic lymphoma kinase (ALK) fusion and resectable non-small cell lung cancer (NSCLC) remain unclear. This study aimed to explore the distribution of ALK fusion variants and prognostic factors in patients with surgically resected NSCLC.
Among the 93 ALK positive surgical patients screened by immunohistochemistry (IHC) or real-time polymerase chain reaction (RT-PCR), 63 patients were confirmed as ALK rearrangement by next-generation sequencing (NGS), including 55 cases of stage I-III and 8 cases of stage IV. Medical records were retrospectively reviewed, the distribution of ALK fusion variants and prognostic factors were analyzed.
All of the 55 early stage patients were histological adenocarcinoma. No other fusion types were found except for echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK). EML4-ALK variant 1 (E13:A20; 25/55, 45.5 %) was the predominant variant type, followed by EML4-ALK variant 3 (E6:A20; 19/55, 34.5 %) and variant 2 (E20:A20; 8/55, 14.5 %). Concomitant mutations occurred in 22 patients (22/55, 40.0 %), which involved in 32 co-mutations from 12 kinds of mutated genes. TP53 mutations were most common in coexisting mutations (13/32, 40.6 %). TP53 mutations were less frequently occurred in variant 1 group (3/25, 12.0 %) than in non-variant 1 group (10/30, 33.3 %, P = 0.064). The median disease-free survival (DFS) of the 55 patients was 22.1 months, and the median overall survival (OS) was not mature at the time of analysis. Multivariable analysis showed that stage T3 and EML4-ALK variant 3 were independent prognostic factors for shorter DFS. Neither TP53 mutations nor any coexisting mutations were related to prognosis.
This study illustrated the patterns of EML4-ALK fusion variants and gene profiles in patients with resected NSCLC. Advanced T stage and EML4-ALK variant 3 were associated with worse prognosis. The role of TP53 mutations in prognosis is worthy of further study.
间变性淋巴瘤激酶（ALK）融合与可切除非小细胞肺癌（NSCLC）的分子特征及预后仍不明确。本研究旨在探讨手术切除的NSCLC患者中ALK融合变异体的分布及预后因素。
在通过免疫组织化学（IHC）或实时聚合酶链反应（RT-PCR）筛选出的93例ALK阳性手术患者中，63例经下一代测序（NGS）确认为ALK重排，其中I-III期55例，IV期8例。对病历进行回顾性分析，分析ALK融合变异体的分布及预后因素。
55例早期患者均为组织学腺癌。除棘皮动物微管相关蛋白样4-间变性淋巴瘤激酶（EML4-ALK）外，未发现其他融合类型。EML4-ALK变异体1（E13:A20；25/55，45.5%）是主要变异类型，其次是EML4-ALK变异体3（E6:A20；19/55，34.5%）和变异体2（E20:A20；8/55，14.5%）。22例患者（22/55，40.0%）发生伴随突变，涉及12种突变基因的32个共突变。TP53突变在共存突变中最常见（13/32，40.6%）。TP53突变在变异体1组中的发生率（3/25，12.0%）低于非变异体1组（10/30，33.3%，P = 0.064）。55例患者的无病生存期（DFS）中位数为22.1个月，分析时总生存期（OS）中位数未成熟。多变量分析显示，T3期和EML4-ALK变异体3是DFS缩短的独立预后因素。TP53突变和任何共存突变均与预后无关。
本研究阐明了手术切除的NSCLC患者中EML4-ALK融合变异体模式和基因特征。T分期晚期和EML4-ALK变异体3与较差的预后相关。TP53突变在预后中的作用值得进一步研究。
