Ma X L, Jia R N, Han K, Zhang Y X
Center of Precision Pathologic Diagnosis, the First Affiliated Hospital of Shandong Second Medical University (Weifang People's Hospital), Weifang 261041, China Department of Basic Medicine, Shandong Second Medical University, Weifang 261053, China.
Center of Precision Pathologic Diagnosis, the First Affiliated Hospital of Shandong Second Medical University (Weifang People's Hospital), Weifang 261041, China.
Zhonghua Bing Li Xue Za Zhi. 2024 Jun 8;53(6):578-584. doi: 10.3760/cma.j.cn112151-20231019-00277.
To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes. There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages (<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all <0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics (>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA (<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups (<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types (<0.05). Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients' age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.
探讨原发性肺腺癌中常见驱动基因变异与其临床特征及组织病理学亚型的相关性。回顾性分析2015年1月至2021年12月在山东省潍坊市人民医院确诊的4995例原发性肺腺癌病例。其中1983例评估了组织病理学亚型；3012例分析了组织病理学亚型与相应驱动基因变异的相关性，包括浸润性非黏液腺癌（INMA）和浸润性黏液腺癌（IMA），以及形态学上的低分化、中分化和高分化腺癌。采用二代测序检测表皮生长因子受体（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原癌基因、受体酪氨酸激酶（ROS1）、间质上皮转化因子（MET）、人表皮生长因子受体2（HER2）或B-Raf原癌基因丝氨酸/苏氨酸激酶（BRAF）驱动基因的变异。患者中男性2384例，女性2611例。EGFR和ALK变异在60岁及以上女性患者中更常见，EGFR在Ⅰ期临床的突变率（25.80%）显著高于其他期（<0.05）。KRAS突变在60岁及以上男性吸烟者中更常见，HER2突变在60岁以下患者中更常见，RET突变在非吸烟者中更常见（均<0.05）。未发现ROS1、MET和BRAF基因变异与其临床特征之间存在相关性（>0.05）。对于组织病理学亚型，在1899例腺泡状腺癌中，EGFR突变率与其他基因相比最高（67.30%）。外显子21 L858R和外显子19缺失是IMA和INMA的主要突变位点，微乳头腺癌中外显子20 T790M的突变率较高（11.63%）。在IMA中，KRAS的总体突变率最高（43.80%），腺泡状腺癌、实体型和IMA中外显子2 G12D和外显子2 G12V的突变率有统计学差异（<0.05）。与中分化和高分化组相比，低分化组各位点的KRAS突变更高（<0.05）。HER2突变在INMA的腺泡状腺癌、乳头状和微乳头状腺癌中更常见。BRAF突变在微乳头腺癌中高于其他类型（<0.05）。原发性肺腺癌中EGFR、ALK、KRAS、HER2和RET的变异与患者年龄、吸烟史和临床分期相关，不同组织病理学亚型的驱动基因突变有所不同。EGFR突变在INMA中占主导地位，而KRAS突变在IMA中占主导地位。
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