Association between the histological subtype of lung adenocarcinoma, EGFR/KRAS mutation status and the ALK rearrangement according to the novel IASLC/ATS/ERS classification
Association between the histological subtype of lung adenocarcinoma, EGFR/KRAS mutation status and the ALK rearrangement according to the novel IASLC/ATS/ERS classification
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DOI：
10.3892/ol.2016.4233
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发表时间：
2016-04-01
期刊：
影响因子：
2.9
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Dong, Yu-Jie;Cai, Yi-Ran;Zhang, Li
本研究旨在探讨表皮生长因子受体（EGFR）/Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）突变、间变性淋巴瘤受体酪氨酸激酶（ALK）重排与肺腺癌（LAC）形态学特征之间的关系，根据国际肺癌研究协会/美国胸科学会/欧洲呼吸学会（IASLC/ATS/ERS）分类在一大组原发性LAC患者中的应用。随机选择了200例在北京胸科医院（中国北京）接受完全切除术的浸润性LAC患者。根据IASLC/ATS/ERS方案，由两名病理学家以5%的增量重新评估样本的形态。通过直接DNA测序检测EGFR和KRAS突变。在Benchmark XT染色仪上通过免疫组织化学筛选ALK重排。数据显示，分别在46.0%（92/200）、9.0%（18/200）和11.5%（23/200）的患者中发现EGFR和KRAS突变以及ALK重排。EGFR/KRAS突变和ALK重排大多是排他性的。然而，1例患者表现出EGFR（外显子20）和KRAS（密码子12）突变共存，另1例患者表现出EGFR突变（外显子21）和ALK基因融合共存。EGFR突变与腺泡型（43/77; 55.8%; P = 0.030）和乳头型（26/49; 53.1%; P = 0.006）亚型密切相关。KRAS突变更常与实体为主亚型（9/52; 17.3%; P = 0.023）和浸润性粘液性LAC（5/10; 50.0%; P = 0.004）相关，与腺泡为主亚型相关性较低（1/77; 1.3%; P = 0.002）。与其他亚型相比，ALK重排更常发生在实性为主亚型中（13/52; 25%; P = 0.002），较少发生在乳头状为主亚型中（1/49; 2.0%; P = 0.004）。ALK重排的肿瘤以印戒细胞为主（7/9; 77.8%; P
The present study aimed to investigate the association between epidermal growth factor receptor (EGFR)/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements and the morphological characteristics of lung adenocarcinoma (LAC), according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification in a large group of patients with primary LAC. A total of 200 patients with invasive LAC who had undergone complete resections at the Beijing Chest Hospital (Beijing, China) were randomly selected. The morphology of the samples was reassessed in 5% increments by two pathologists, according to the IASLC/ATS/ERS scheme. EGFR and KRAS mutations were tested by direct DNA sequencing. ALK rearrangements were screened by immunohistochemistry on a Benchmark XT stainer. The data revealed that EGFR and KRAS mutations, and ALK rearrangements were identified in 46.0% (92/200), 9.0% (18/200) and 11.5% (23/200) of the patients, respectively. The EGFR/KRAS mutations and ALK rearrangements were mostly exclusive. However, 1 patient exhibited the coexistence of the EGFR (at exon 20) and KRAS (codon 12) mutations, and another patient exhibited the coexistence of the EGFR mutation (at exon 21) and the ALK gene fusion. EGFR mutations were indicated to be closely associated with the acinar predominant (43/77; 55.8%; P=0.030) and papillary predominant (26/49; 53.1%; P=0.006) subtypes. KRAS mutations were more commonly associated with the solid predominant subtype (9/52; 17.3%; P=0.023) and invasive mucinous LAC (5/10; 50.0%; P=0.004), and less commonly associated with the acinar predominant subtype (1/77; 1.3%; P=0.002). ALK rearrangements more commonly occurred in the solid predominant subtype compared with other subtypes (13/52; 25%; P=0.002), and less commonly occurred in the papillary predominant subtype (1/49; 2.0%; P=0.004). Tumors harboring ALK rearrangements were characterized by signet-ring cell (7/9; 77.8%; P