Distribution of intestinal stem cell markers in colorectal precancerous lesions
Distribution of intestinal stem cell markers in colorectal precancerous lesions
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DOI：
10.1111/his.12787
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发表时间：
2016-03-01
期刊：
影响因子：
6.4
通讯作者：
Kang, Gyeong Hoon
中科院分区：
文献类型：
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作者：
Jang, Bo Gun;Kim, Hye Sung;Kang, Gyeong Hoon
目的LGR5、ASCL2、EPHB2和OLFM4等肠道干细胞(ISC)标志物在结直肠癌中的临床意义已被广泛研究。然而，对它们在癌前病变中的表达知之甚少。方法和结果逆转录-聚合酶链式反应(RT-PCR)分析显示，与其他病变相比，所有ISC标志物在伴低级别异型增生(CALGs)的常规腺瘤中的表达均显著上调。RNA原位杂交证实，CALGs强而弥漫地表达所有ISC标记，提示为干细胞样表型。然而，在正常结肠粘膜、增生性息肉和固有性锯齿状腺瘤中，LGR5(+)细胞仅局限于隐窝底部，并显示ISC标记的有组织表达。值得注意的是，在传统的锯齿状腺瘤中，LGR5和ASCL2的表达与正常隐窝一样局限于异位隐窝，而EPHB2和OLFM4的表达呈弥漫性分布，提示具有祖细胞样特征。结论ISC标记物的表达和分布特征可能有助于了解各种类型的结直肠癌癌前病变中干/祖细胞的组织结构。
AimsIntestinal stem cell (ISC) markers such as LGR5, ASCL2, EPHB2 and OLFM4, and their clinical implications have been studied extensively in colorectal cancers (CRCs). However, little is known about their expression in precancerous lesions of CRCs. Here, we investigated the expression and distribution of ISC markers in serrated polyps and conventional adenomas.Methods and resultsReverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that all ISC markers were up-regulated significantly in conventional adenomas with low-grade dysplasia(CALGs) compared with other lesions. RNA in-situ hybridization confirmed that CALGs exhibitedstrong and diffuse expression of all ISC markers, which indicate a stem cell-like phenotype. However, normal colonic mucosa, hyperplastic polyps and sessile serrated adenomas harboured LGR5(+) cells that were confined to the crypt base and demonstrated an organized expression of ISC markers. Notably, in traditional serrated adenomas, expression of LGR5 and ASCL2 was localized to the ectopic crypts as in the normal crypts, but expression of EPHB2 and OLFM4 was distributed in a diffuse manner, which is suggestive of a progenitor-like features.ConclusionsThe expression and distribution profile of ISC markers possibly provides insights into the organization of stem and progenitor-like cells in each type of precancerous lesion of CRC.