Early KRAS oncogenic driver mutations in nonmucinous tissue of congenital pulmonary airway malformations as an indicator of potential malignant behavior
Early KRAS oncogenic driver mutations in nonmucinous tissue of congenital pulmonary airway malformations as an indicator of potential malignant behavior
复制标题
DOI：
10.1016/j.humpath.2020.07.015
复制
发表时间：
2020-09-01
期刊：
影响因子：
3.3
通讯作者：
von der Thusen, Jan H.
中科院分区：
文献类型：
--
作者：
Hermelijn, Sergei M.;Wolf, Janina L.;von der Thusen, Jan H.
恶变的可能性是一些从业者切除无症状先天性肺道畸形(CPAM)的最常见原因。我们的目的是研究各种免疫组织化学(IHC)和基因组生物标记物预测CPAM中粘液增殖(MPS)的可能性。使用一组区分标记(TTF1/CDX2/CC10/MUC2/MUC5AC/p16/P53/DICER1)重新评估CPAM组织样本并进行IHC分析。在每个样本中，使用半定量方法分别评估正常肺组织、CPAM和MP组织中IHC染色的强度。同样，对已知的成人肺驱动基因突变，包括KRAS/BRAF/EGFR/ERBB2，在所有患有MP的样本和没有MP的CPAM组织的对照样本中进行了下一代靶向测序。我们分析了25个CPAM 1型和25个CPAM 2型的样本，发现11个样本中有MPS。均表现为MUC5AC强表达，且在MP及邻近非粘液性CPAM组织中均存在KRAS突变，而周围正常肺组织均为阴性。相比之下，在不到一半(12个中的5个)缺乏MP的对照样本中，CPAM组织也携带KRAS突变。非粘液性CPAM组织中的KRAS突变可以识别具有潜在恶变潜能的病变，并可能指导组织病理学评估和患者随访。(C)2020年提交人(S)。由爱思唯尔公司出版。
The potential for malignant degeneration is the most common reason for some practitioners to resect asymptomatic congenital pulmonary airway malformations (CPAMs). We aimed to investigate the potential of various immunohistochemical (IHC) and genomic biomarkers to predict the presence of mucinous proliferations (MPs) in CPAM. Archival CPAM tissue samples were re-assessed and underwent IHC analysis using a panel of differentiating markers (TTF1/CDX2/CC10/MUC2/MUC5AC/p16/p53/DICER1). In each sample, intensity of IHC staining was assessed separately in normal lung tissue, CPAM, and MP tissue, using a semiquantitative approach. Likewise, next-generation targeted sequencing of known adult lung driver mutations, including KRAS/BRAF/EGFR/ERBB2, was performed in all samples with MP and in control samples of CPAM tissue without MP. We analyzed samples of 25 CPAM type 1 and 25 CPAM type 2 and found MPs in 11 samples. They were all characterized by strong MUC5AC expression, and all carried a KRAS mutation in the MP and adjacent nonmucinous CPAM tissue, whereas the surrounding normal lung tissue was negative. By contrast, in less than half (5 out of 12) control samples lacking MP, the CPAM tissue also carried a KRAS mutation. KRAS mutations in nonmucinous CPAM tissue may identify lesions with a potential for malignant degeneration and may guide histopathological assessment and patient follow-up. (C) 2020 The Author(s). Published by Elsevier Inc.