Dong Yu-Jie, Cai Yi-Ran, Zhou Li-Juan, Su Dan, Mu Jing, Chen Xue-Jing, Zhang L I
Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China.
Oncol Lett. 2016 Apr;11(4):2552-2558. doi: 10.3892/ol.2016.4233. Epub 2016 Feb 17.
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<0.0001) and cribriform (7/12; 58.3%; P<0.0001) patterns. The association between the mutation status and histological subtype in LAC was distinct. The predominant subtype according to the IASLC/ATS/ERS classification provided important information for gene mutations and integrated clinical findings to improve the treatment of LAC patients.
本研究旨在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，在一大群原发性肺腺癌（LAC）患者中，调查表皮生长因子受体（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）重排与肺腺癌形态学特征之间的关联。随机选取了200例在北京胸科医院（中国北京）接受了完整切除手术的浸润性LAC患者。两名病理学家根据IASLC/ATS/ERS方案，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）的患者中检测到EGFR和KRAS突变以及ALK重排。EGFR/KRAS突变和ALK重排大多相互排斥。然而，1例患者同时存在EGFR（第20外显子）和KRAS（密码子12）突变，另1例患者同时存在EGFR突变（第21外显子）和ALK基因融合。结果表明，EGFR突变与腺泡为主型（43/77；55.8%；P = 0.030）和乳头为主型（26/49；53.1%；P = 0.006）亚型密切相关。KRAS突变更常见于实体为主型亚型（9/52；17.3%；P = 0.023）和浸润性黏液性LAC（5/10；50.0%；P = 0.004），较少见于腺泡为主型亚型（1/77；1.3%；P = 0.002）。与其他亚型相比，ALK重排更常见于实体为主型亚型（13/52；25%；P = 0.002），较少见于乳头为主型亚型（1/49；2.0%；P = 0.004）。存在ALK重排的肿瘤以印戒细胞（7/9；77.8%；P < 0.0001）和筛状（7/12；58.3%；P < 0.0001）模式为特征。LAC中突变状态与组织学亚型之间的关联是不同的。根据IASLC/ATS/ERS分类的主要亚型为基因突变和综合临床发现提供了重要信息，以改善LAC患者的治疗。
