Baudhuin Linnea M, Burgart Lawrence J, Leontovich Olga, Thibodeau Stephen N
Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, 200 First St. SW, 920 Hilton Building, Rochester, MN 55905, USA.
Fam Cancer. 2005;4(3):255-65. doi: 10.1007/s10689-004-1447-6.
It is now generally recognized that a specific subset of those patients clinically defined as having hereditary non polyposis colon cancer (HNPCC) have germline mutations in any one of several genes involved in DNA mismatch repair (MMR). This important subset of HNPCC families is now defined as having Lynch syndrome. A considerable amount of data has shown that tumors from patients with Lynch syndrome have characteristic features resulting from the underlying molecular involvement of defective MMR, that is, the presence of microsatellite instability (MSI) and the absence of MMR protein expression by immunohistochemistry (IHC). As a result, identifying patients with Lynch syndrome can now be accomplished by testing tumors for these tumor-related changes. Together, MSI and IHC are powerful tools that help identify individuals at risk for having Lynch syndrome and to distinguish these cases from HNPCC cases with other hereditary gene defects. Furthermore, IHC analysis provides valuable clues as to which MMR gene is mutated, allowing for comprehensive mutational analyses of that gene. Here, we discuss the current and historical perspectives regarding MSI and IHC analyses in tumors from sporadic colon cancer and from patients with Lynch syndrome. Given this background, we also provide a testing strategy for the identification of patients at risk for Lynch syndrome and subsequent gene testing.
现在人们普遍认识到，在临床上被定义为患有遗传性非息肉病性结直肠癌（HNPCC）的患者中，有一个特定亚组在参与DNA错配修复（MMR）的几个基因中的任何一个基因中存在种系突变。HNPCC家族的这一重要亚组现在被定义为患有林奇综合征。大量数据表明，林奇综合征患者的肿瘤具有由缺陷MMR的潜在分子参与导致的特征性特征，即微卫星不稳定性（MSI）的存在以及通过免疫组织化学（IHC）检测不到MMR蛋白表达。因此，现在可以通过检测肿瘤的这些与肿瘤相关的变化来识别林奇综合征患者。MSI和IHC共同构成了强大的工具，有助于识别有患林奇综合征风险的个体，并将这些病例与具有其他遗传性基因缺陷的HNPCC病例区分开来。此外，IHC分析为哪个MMR基因发生突变提供了有价值的线索，从而能够对该基因进行全面的突变分析。在此，我们讨论了散发性结肠癌和林奇综合征患者肿瘤中MSI和IHC分析的当前及历史观点。鉴于此背景，我们还提供了一种检测策略，用于识别有林奇综合征风险的患者并进行后续基因检测。
