Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Pathology, Southeast University, Zhongda Hospital, Nanjing, China.
Thorac Cancer. 2020 Jan;11(1):103-112. doi: 10.1111/1759-7714.13208. Epub 2019 Nov 6.
Distinction in the mutational profile between the common histological types, lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) has been well-established. However, comprehensive mutation profiles of the predominant histological subtypes within LUAD and LUSC remains elusive.
We analyzed the mutational profile of 318 Chinese NSCLC patients of adenocarcinoma and squamous cell carcinoma predominant subtypes from seven hospitals using capture-based ultra-deep sequencing of 68 lung cancer-related genes.
Of the 318 NSCLC patients, 215 were diagnosed with LUAD and 103 with LUSC. Adenocarcinoma in situ and acinar adenocarcinoma were the most predominant subtypes of LUAD. On the other hand, keratinizing squamous cell carcinoma was the most predominant subtype of LUSC. Among the LUAD subtypes, EGFR sensitizing mutations were most prevalent in the invasive lepidic subtype. More than half of the patients with preinvasive adenocarcinoma in situ, minimally invasive, acinar, micropapillary and papillary subtypes were also EGFR-mutants. Patients with colloidal, invasive mucinous, and fetal subtypes had the least number of EGFR mutations. Moreover, KRAS mutations were prevalent in patients with invasive mucinous, colloid, enteric and solid subtypes. A total of 90% of the LUSC patients harbor mutations in TP53, wherein all patients except five with nonkeratinizing were TP53 mutants. PIK3CA amplifications were most prevalent in keratinizing, followed by basaloid and nonkeratinizing subtypes.
These data suggest that the mutational profiles among the predominant histological subtypes were very distinct, which provided a reliable tool to improve treatment decisions.
肺腺癌（LUAD）和鳞状细胞肺癌（LUSC）这两种常见组织学类型之间的突变特征差异已经得到了充分证实。然而，LUAD 和 LUSC 中主要组织学亚型的综合突变特征仍然难以捉摸。
我们分析了来自 7 家医院的 318 例中国 NSCLC 患者（主要为腺癌和鳞状细胞癌）的突变特征，这些患者采用了 68 个肺癌相关基因的基于捕获的超深度测序。
在 318 例 NSCLC 患者中，215 例诊断为 LUAD，103 例诊断为 LUSC。原位腺癌和腺泡状腺癌是 LUAD 最主要的亚型。另一方面，角化鳞状细胞癌是 LUSC 最主要的亚型。在 LUAD 亚型中，表皮生长因子受体（EGFR）敏感突变在浸润性贴壁亚型中最为常见。超过一半的浸润前原位腺癌、微浸润、腺泡、微乳头和乳头亚型患者也是 EGFR 突变型。具有胶样、浸润性黏液、胎儿亚型的患者 EGFR 突变数量最少。此外，KRAS 突变在浸润性黏液、胶样、肠型和实体型患者中较为常见。90%的 LUSC 患者携带 TP53 突变，其中除了 5 名非角化患者外，其余均为 TP53 突变。PIK3CA 扩增在角化、基底样和非角化亚型中最为常见。
这些数据表明，主要组织学亚型之间的突变特征非常不同，为改善治疗决策提供了可靠的工具。
