Genetic and Immunohistochemical Studies Investigating the Histogenesis of Neuroendocrine and Carcinomatous Components of Combined Neuroendocrine Carcinoma
Genetic and Immunohistochemical Studies Investigating the Histogenesis of Neuroendocrine and Carcinomatous Components of Combined Neuroendocrine Carcinoma
复制标题
DOI：
10.1245/s10434-019-07268-0
复制
发表时间：
2019-06-01
影响因子：
3.7
通讯作者：
Kuwano, Hiroyuki
中科院分区：
文献类型：
--
作者：
Iijima, Misaki;Yokobori, Takehiko;Kuwano, Hiroyuki
背景肺联合神经内分泌癌（NECs）包括NEC和非NEC成分，如腺癌和鳞癌。表皮生长因子受体（EGFR）的突变通常在非NEC中观察到，但在散发性NEC中非常罕见，几乎总是有p53突变。因此，我们假设以下的研究概念：突变分析EGFR和p53的组合NEC组织中的每一个组成部分，可以提供重要的信息，这些组成部分是否来自相同的肿瘤细胞或偶然出现的碰撞cancer.MethodsWe比较了突变的EGFR和p53的激光显微镜下的NEC和非NEC从肺部的8例合并NEC的影响。我们研究了EGFR和NEC标志物的表达，在联合NEC的免疫组化simmuno.Results5的8例合并NEC有相同的突变EGFR和/或p53在两个非NEC和NEC。1例仅在非NEC组分中存在EGFR突变，2例不存在这些突变。在非NEC和NEC之间的边界区域观察到替代转化。相同EGFR突变的非NEC中激活EGFR的信号比NEC components.ConclusionsOur的研究表明，肺癌合并NEC，这是部分由非NEC上皮癌NEC的转化背后的机制。
BackgroundLung combined neuroendocrine carcinomas (NECs) comprise NEC and non-NEC components, such as adenocarcinoma and squamous cell carcinoma. Mutation of epidermal growth factor receptor (EGFR) often is observed in non-NEC but is very rare in sporadic NEC, which almost always has p53 mutation. Therefore, we hypothesized the following research concept: mutation analysis of EGFR and p53 in each component of combined NEC tissues can provide important information on whether such components originate from the same tumor cells or incidentally arise as collision cancers.MethodsWe compared the mutations of EGFR and p53 in laser-microdissected NEC and non-NEC from lungs of eight cases affected by combined NEC. We examined the expression of EGFR and NEC markers in the combined NECs by immunohistochemistry.ResultsFive of eight cases of combined NEC had the same mutations of EGFR and/or p53 in both non-NEC and NEC. One case had EGFR mutation in only the non-NEC component, and two cases did not have these mutations. Replacement transformation was observed in borderline areas between non-NEC and NEC. The signal of activated EGFR in non-NEC with the same EGFR mutation was more intense than that in NEC components.ConclusionsOur study suggests the mechanism behind the carcinogenesis of lung combined NEC, which is partially caused by the transformation from epithelial carcinoma of non-NEC to NEC.