Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer
Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer
复制标题
DOI：
10.3748/wjg.v20.i15.4230
复制
发表时间：
2014-04-21
影响因子：
4.3
通讯作者：
Kang, Gyeong Hoon
中科院分区：
文献类型：
--
作者：
Kim, Jung Ho;Kang, Gyeong Hoon
具有高水平微卫星不稳定性（MSI-H）的结直肠癌（CRC）是临床病理学上独特的肿瘤，其特征在于女性占优势、近端结肠定位、低分化、粘液组织学、肿瘤浸润淋巴细胞、克罗恩样淋巴反应和良好预后。就其分子特征而言，MSI-H CRC是与各种遗传和表观遗传改变相关的异质性肿瘤，包括DNA错配修复缺陷、靶微卫星突变、BRAF突变、CpG岛甲基化表型高（CIMP-H）状态和低水平的基因组低甲基化。MSI-H CRC的分子异质性也取决于种族差异;例如，在东亚国家，与西方国家相比，在MSI-H CRC中观察到CIMP-H和BRAF突变频率相对较低。尽管MSI-H CRC的预后特征包括患者的有利生存和辅助化疗的低获益，但基于MSI-H CRC的分子异质性，可能存在预后差异。在此，我们回顾并讨论了MSI-H CRCs的分子和预后特征，以及几种推定的预后或预测分子标记物，包括HSP 110表达、β 2-微球蛋白突变、肌球蛋白1a表达、CDX 2/CK 20表达、SMAD 4表达、CIMP状态和LINE-1甲基化水平。(C)2014百世登出版集团有限公司有限公司All rights reserved.
Colorectal cancers (CRCs) with a high level of microsatellite instability (MSI-H) are clinicopathologically distinct tumors characterized by predominance in females, proximal colonic localization, poor differentiation, mucinous histology, tumor-infiltrating lymphocytes, a Crohn's-like lymphoid reaction and a favorable prognosis. In terms of their molecular features, MSI-H CRCs are heterogeneous tumors associated with various genetic and epigenetic alterations, including DNA mismatch repair deficiency, target microsatellite mutations, BRAF mutations, a CpG island methylator phenotype-high (CIMP-H) status, and a low level of genomic hypomethylation. The molecular heterogeneity of MSI-H CRCs also depends on ethnic differences; for example, in Eastern Asian countries, relatively low frequencies of CIMP-H and BRAF mutations have been observed in MSI-H CRCs compared to Western countries. Although the prognostic features of MSI-H CRCs include a favorable survival of patients and low benefit of adjuvant chemotherapy, there may be prognostic differences based on the molecular heterogeneity of MSI-H CRCs. Here, we have reviewed and discussed the molecular and prognostic features of MSI-H CRCs, as well as several putative prognostic or predictive molecular markers, including HSP110 expression, beta2-microglobulin mutations, myosin 1a expression, CDX2/CK20 expression, SMAD4 expression, CIMP status and LINE-1 methylation levels. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.