| Rina Na,Wei Luan,Yinzai He,Yanwei Gao,Nier Cha,Baoqin Jia. Relationship between molecular changes in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in lung adenocarcinoma. Oncol Transl Med, 2021, 7: 155-159. |
| 肺腺癌相关分子靶向特征和临床病理预后因素的关系 |
| Relationship between molecular changes in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in lung adenocarcinoma |
| Received:June 21, 2020 Revised:August 15, 2021 |
| DOI：10.1007/s10330-020-0440-0 |
| 中文关键词: 肺癌，组织学亚型，预后，EML4-ALK，EGFR。 |
| 英文关键词: lung cancer; histological subtypes; prognosis; the echinoderm microtubule-associated protein-like 4 gene-ALK variant (EML4-ALK); epidermal growth factor receptor (EGFR) |
| 基金项目:本研究受内蒙古自治区卫生健康委员会科研计划资助 |
| Author Name | Affiliation | E-mail | | Rina Na | Department of General Surgery, Inner Mongolia People''s Hospital | luan1977@126.com | | Wei Luan | Department of Oncology, Inner Mongolia People''s Hospital | | | Yinzai He | Department of Surgical Oncology, Inner Mongolia People''s Hospital | | | Yanwei Gao | Department of Surgical Oncology, Inner Mongolia People''s Hospital | | | Nier Cha | Department of Surgical Oncology, Inner Mongolia People''s Hospital | | | Baoqin Jia* | Department of Surgical Oncology, Inner Mongolia People''s Hospital | 13604715646@qq.com |
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| 中文摘要: |
| 目的：肺腺癌相关EGFR、ALK基因突变和临床及病理学预后因素分析。
方法：回顾性分析我中心2007年1月至2014年1月间经根治性手术切除、病理诊断为肺腺癌的病例158例；以2015版WHO肺腺癌新分型标准对组织切片重新进行评估，使用5%增量记录每种组织学成分，按全面组织学亚型进行组织学分型，并对生存病例随访；应用RT-PCR法和直接DNA测序法检出肿瘤组织内EGFR基因18、19、20及21号外显子突变和EML4-ALK融合基因的情况。运用SPSS统计软件（17.0）对实验数据进行统计分析。
结果：
158例病例中，男70例、女88例，平均年龄59.1岁（30～77岁），非吸烟者120例（75.9%），IA期33例，IB期30例，ⅡA期21例，ⅡB期23例，ⅢA期31例，ⅢB期10例，Ⅳ10例，包含浸润前腺癌25例，浸润性腺癌中贴壁为主（13例）、腺泡状为主（66例）、乳头状为主（13例）、实性为主（25例）等病理亚型均有分布。随访时间为22～112个月，失访4例。各组织学亚型预后不同。浸润前腺癌的5年DFS和5年OS为100%。贴壁为主、腺泡状为主和乳头状为主腺癌的5年OS分别为84.6%、72.7%和76.9%。实性为主腺癌和黏液腺癌5年OS为32.0%、36.4%。
2、检测158例样本中，EGFR突变69例，突变率43.7%；以19号外显子突变（50.6%）和21号外显子突变（37.9%）为主，其中女性、非吸烟患者具有更高突变率（P＜0.05）；年龄、肿瘤大小、分期、肺膜受累、淋巴结转移均未发现与EGFR基因突变相关；组织学亚型分析发现，EGFR突变主要集中于贴壁型(53.8％)、腺泡型腺癌(50.0％)，而实性为主腺癌(28.0％)、黏液腺癌(27.2％)则罕见。EML4-ALK基因融合突变率5.69%，常见于年轻的非吸烟患者（P＜0.05），粘液腺癌及实性为主腺癌中融合突变更常见；未发现双突变。
结论：肺腺癌各组织学亚型预后不同，其与EGFR基因、EML4-ALK基因突变状态相关，贴壁为主、腺泡状为主腺癌EGFR突变率高，而实性为主腺癌、黏液腺癌中EML4-ALK基因融合突变更常见。EGFR突变常见于女性、非吸烟患者，EML4-ALK基因融合突变常见于年轻的非吸烟患者。 |
| 英文摘要: |
| Objective: This study aimed to analyze the relationship between the mutations in epidermal growth factor
receptor (EGFR) and anaplastic lymphoma kinase (ALK) and their impact on the prognosis and treatment
of lung adenocarcinoma.
Methods: A total of 158 cases of lung adenocarcinoma reported between January 2007 and January
2014 were retrospectively analyzed. These tumors were resected using radical pneumonectomy and
underwent pathology-based diagnosis at our institution (Inner Mongolia People’s Hospital, Hohhot, China).
The tissue sections were evaluated using the updated World Health Organization classification of lung
adenocarcinomas (2015 version), with each histological component recorded in 5% increments. The
histological subtypes were classified, and any surviving cases were followed up. The reverse transcriptionpolymerase
chain reaction (RT-PCR) and direct DNA sequencing were used to evaluate mutations in exons
18, 19, 20, and 21 in the EGFR gene, and the echinoderm microtubule-associated protein-like 4 gene-ALK
variant (EML4-ALK) fusions were detected using sequencing.
Results: Our cohort included 25 patients with pre-invasive adenocarcinoma, 13 patients with lepidic, 66
patients with acinar, 13 patients with papillary, and 25 patients with solid infiltrative adenocarcinoma with
the remaining cases presenting with a variety of pathological subtypes. The prognosis of each histological
subtype was different with the 5-year disease-free survival and 5-year overall survival (OS) of pre-invasion
adenocarcinoma at 100%; the 5-year OS of lepidic, acinar, and papillary adenocarcinoma patients was
only 84.6%, 72.7%, and 76.9%, respectively. The 5-year OS of solid and mucinous adenocarcinomas were
32.0% and 36.4%, respectively. EGFR mutation was detected in 69 cases with a mutation rate of 43.7% and
majority of these mutations were found in exons 19 (50.6%) and 21 (37.9%), with women and non-smokers
shown to experience a higher mutation rate (P < 0.05). However, histological subtype analysis showed that
EGFR mutations were primarily found in adenocarcinomas. Most of these mutations were found in lepidic
(53.8%) or acinar adenocarcinomas (50.0%), whereas these mutations were rare in both solid (28.0%) and
mucinous adenocarcinoma (27.2%). The fusion mutation rate in the EML4-ALK gene was 5.69%, and was
most common in young, nonsmoking patients (P < 0.05).
Conclusion: The prognosis of patients in each lung adenocarcinoma subtype is different, and these
outcomes are likely related to mutations in the EGFR and EML4-ALK genes. EGFR mutation rates are
higher in lepidic and acinar adenocarcinomas, whereas EML4-ALK gene fusion mutations are more
common in solid and mucinous adenocarcinoma. EGFR mutations are more common in female and nonsmoking
patients, whereas EML4-ALK fusions are more common in young, non-smoking patients. |
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