Macroscopic and microscopic morphology and molecular profiling to distinguish heterogeneous traditional serrated adenomas of the colorectum

Macroscopic and microscopic morphology and molecular profiling to distinguish heterogeneous traditional serrated adenomas of the colorectum
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DOI:
10.1111/den.13603
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发表时间:
2020-09-01
影响因子:
5.3
通讯作者:
Nagayama, Satoshi
Nagayama, Satoshi
中科院分区:
医学2区
文献类型:
--
作者:
Chino, Akiko;Kawachi, Hiroshi;Nagayama, Satoshi

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目的结直肠锯齿状病变的组织学形态复杂,有些组包括不同分子生物学亚型。本研究旨在描述以传统锯齿状腺瘤(TSA)成分为主的异质组织学锯齿状病变。方法根据内镜和组织学特点选择有代表性的病变。如果病变有一个以上的组成部分,每个不同的结构部分被认为是一个单独的样本。从60例177例患者的皮损中提取DNA,扩增BRAF和K/NRAS突变。结果TSA分为4类:无蒂锯齿状病变伴TSA(SA-1)、微泡增生性息肉伴TSA(SA-2)、未分类腺瘤伴TSA(SA-3)和常规腺瘤伴TSA(SA-4)。在内镜检查中,SA-1病变具有小的淡红色隆起的柄部隆起形态; SA-2病变具有带蒂外观,在柄部处具有白色粘膜成分; SA-3病变具有平坦扩展边缘包围的柄部隆起成分; SA-4病变具有混合腺瘤形态。19例SA-1和-2型病变中有18例(95%)有BRAF突变,所有SA-3和-4型病变均有K/NRAS突变。结论传统型锯齿状腺瘤根据其分子特征可分为两种表型:BRAF突变的微泡型锯齿状腺瘤(SA-1和SA-2)和K/NRAS突变的管状型锯齿状腺瘤/传统型腺瘤(SA-3和SA-4)。每个亚型具有特征性的宏观和微观形态,并且在内窥镜检查中是不同的。
Objectives Serrated lesions of the colorectum often have complex histological morphology, and some groups include subtypes with different molecular biology. This study aimed to characterize serrated lesions with heterogeneous histology that was dominated by a traditional serrated adenoma (TSA) component. Methods Representative lesions were selected based on both endoscopic and histological features. If a lesion had more than one component, each of the different structural parts was considered as a separate sample. DNA was extracted from 177 samples of 60 lesions and amplified to screen forBRAFandK/NRASmutations. Results Heterogeneous TSA samples were classified into four categories: sessile serrated lesion with TSA (SA-1); TSAs with microvesicular hyperplastic polyp (SA-2); TSAs with unclassified adenoma, characterized by tubulo-serrated histology (SA-3); and TSAs with conventional adenomas (SA-4). On endoscopy, SA-1 lesions had sessile-elevated morphology with the small reddish elevations; SA-2 lesions had a pedunculated appearance with a whitish mucosal component at the stalk; SA-3 lesions had a sessile-elevated component surrounded by flat spreading margins; and SA-4 lesions had mixed adenomatous morphology. Eighteen of the 19 category SA-1 and -2 lesions (95%) hadBRAFmutations, and all of the SA-3 and -4 lesions hadK/NRASmutations. Conclusions Traditional serrated adenomas were classified into two phenotypes according to their molecular characteristics: microvesicular serrated subtypes withBRAFmutations (SA-1 and -2 lesions) and subtypes containing tubulo-serrated/conventional adenoma withK/NRASmutations (SA-3 and -4 lesions). Each subtype had characteristic macroscopic and microscopic morphologies and was distinct on endoscopy.