瑞士东北部肺腺癌患者致癌驱动基因突变频率分析及其与临床病理特征的相关性
Analysis of the frequency of oncogenic driver mutations and correlation with clinicopathological characteristics in patients with lung adenocarcinoma from Northeastern Switzerland.
作者信息
Grosse Alexandra, Grosse Claudia, Rechsteiner Markus, Soltermann Alex
机构信息
Institute of Pathology and Molecular Pathology, Clinical Pathology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
Institute of Pathology, Kepler University Hospital, Krankenhausstraße 9, 4021, Linz, Austria.
出版信息
Diagn Pathol. 2019 Feb 11;14(1):18. doi: 10.1186/s13000-019-0789-1.
BACKGROUND
Molecular testing of lung adenocarcinoma for oncogenic driver mutations has become standard in pathology practice. The aim of the study was to analyze the EGFR, KRAS, ALK, RET, ROS1, BRAF, ERBB2, MET and PIK3CA mutational status in a representative cohort of Swiss patients with lung adenocarcinoma and to correlate the mutational status with clinicopathological patient characteristics.
METHODS
All patients who underwent molecular testing of newly diagnosed lung adenocarcinoma during a 4-year period (2014-2018) were included. Molecular analyses were performed with Sanger sequencing (n = 158) and next generation sequencing (n = 311). ALK, ROS1 and RET fusion gene analyses were also performed with fluorescence in situ hybridization and immunohistochemistry/immunocytochemistry. Demographic and clinical data were obtained from the medical records.
RESULTS
Of 469 patients with informative EGFR mutation analyses, 90 (19.2%) had EGFR mutations. KRAS mutations were present in 33.9% of the patients, while 6.0% of patients showed ALK rearrangement. BRAF, ERBB2, MET and PIK3CA mutations and ROS1 and RET rearrangements were found in 2.6%, 1.9%, 1.9%, 1.5%, 1.7% and 0.8% of the patients, respectively. EGFR mutation was significantly associated with female gender and never smoking status. ALK translocations were more frequent in never smokers, while KRAS mutations were more commonly found in ever smokers. The association between KRAS mutational status and female gender was statistically significant only on multivariate analysis after adjusting for smoking.
CONCLUSION
The EGFR mutation rate in the current study is among the higher previously reported mutation rates, while the frequencies of KRAS, BRAF, ERBB2 and PIK3CA mutations and ALK, ROS1 and RET rearrangements are similar to the results of previous reports. EGFR and KRAS mutations were significantly associated with gender and smoking. ALK rearrangements showed a significant association with smoking status alone.
背景
对肺腺癌进行致癌驱动基因突变的分子检测已成为病理学实践中的标准操作。本研究的目的是分析瑞士肺腺癌患者代表性队列中的表皮生长因子受体（EGFR）、 Kirsten 大鼠肉瘤病毒癌基因（KRAS）、间变性淋巴瘤激酶（ALK）、转染重排（RET）、ROS1、B-Raf原癌基因（BRAF）、表皮生长因子受体2（ERBB2）、间质-上皮转化因子（MET）和磷脂酰肌醇-3激酶催化亚基α（PIK3CA）的突变状态，并将突变状态与患者的临床病理特征相关联。
方法
纳入在4年期间（2014 - 2018年）对新诊断的肺腺癌进行分子检测的所有患者。采用桑格测序法（n = 158）和新一代测序法（n = 311）进行分子分析。还采用荧光原位杂交以及免疫组织化学/免疫细胞化学进行ALK、ROS1和RET融合基因分析。从病历中获取人口统计学和临床数据。
结果
在469例有信息可用的EGFR突变分析患者中，90例（19.2%）有EGFR突变。33.9%的患者存在KRAS突变，而6.0%的患者显示ALK重排。BRAF、ERBB2、MET和PIK3CA突变以及ROS1和RET重排在患者中的发生率分别为2.6%、1.9%、1.9%、1.5%、1.7%和0.8%。EGFR突变与女性性别和从不吸烟状态显著相关。ALK易位在从不吸烟者中更常见，而KRAS突变在曾经吸烟者中更常见。仅在调整吸烟因素后的多变量分析中，KRAS突变状态与女性性别之间的关联具有统计学意义。
结论
本研究中的EGFR突变率在先前报道的较高突变率之中，而KRAS、BRAF、ERBB2和PIK3CA突变以及ALK、ROS1和RET重排的频率与先前报道的结果相似。EGFR和KRAS突变与性别和吸烟显著相关。ALK重排仅与吸烟状态显著相关。
Zotero 插件