Molecular genetics of microsatellite-unstable colorectal cancer for pathologists.
Molecular genetics of microsatellite-unstable colorectal cancer for pathologists.
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DOI：
10.1186/s13000-017-0613-8
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发表时间：
2017-03-04
影响因子：
2.6
通讯作者：
Frankel WL
中科院分区：
文献类型：
--
作者：
Chen W;Swanson BJ;Frankel WL
微卫星不稳定性结直肠癌(CRC)是由DNA错配修复缺陷(DMMR)引起的，约占美国所有结直肠癌的15%。这些微卫星不稳定的CRC代表了一组具有不同肿瘤发生途径的异质性疾病。这些组之间有重叠的临床病理特征，但也存在许多重要的差异。因此，确定dMMR的病因对于正确的患者管理和随访是至关重要的。MLH1MMR基因的表观失活(散发性微卫星不稳定性)和MMR基因的胚系突变(Lynch综合征，LS)是结直肠癌微卫星不稳定性的两种最常见的发病机制。然而，在通过筛查试验确定的dMMR CRC病例的子集中，目前的基因分析没有发现与LS相关的已知基因改变。当dMMR的病因不明时，它会导致患者焦虑，并给临床管理带来挑战。关键是要将LS患者与其他患有dMMR的肿瘤患者区分开来，以便为患者及其家人采用适当的筛查方案，目的是在挽救生命的同时避免不必要的焦虑和成本。现就dMMR癌的主要发病途径、临床病理特点及筛查建议作一综述。此外，我们还包括MMR免疫组织化学解释的常见问题。
Microsatellite-unstable colorectal cancers (CRC) that are due to deficient DNA mismatch repair (dMMR) represent approximately 15% of all CRCs in the United States. These microsatellite-unstable CRCs represent a heterogenous group of diseases with distinct oncogenesis pathways. There are overlapping clinicopathologic features between some of these groups, but many important differences are present. Therefore, determination of the etiology for the dMMR is vital for proper patient management and follow-up. Epigenetic inactivation of MLH1 MMR gene (sporadic microsatellite-unstable CRC) and germline mutation in an MMR gene (Lynch syndrome, LS) are the two most common mechanisms in the pathogenesis of microsatellite instability in CRC. However, in a subset of dMMR CRC cases that are identified by screening tests, no known LS-associated genetic alterations are appreciated by current genetic analysis. When the etiology for dMMR is unclear, it leads to patient anxiety and creates challenges for clinical management. It is critical to distinguish LS patients from other patients with tumors due to dMMR, so that the proper screening protocol can be employed for the patients and their families, with the goal to save lives while avoiding unnecessary anxiety and costs. This review summarizes the major pathogenesis pathways of dMMR CRCs, their clinicopathologic features, and practical screening suggestions. In addition, we include frequently asked questions for MMR immunohistochemistry interpretation.