Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome - Part I. The utility of immunohistochemistry
Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome - Part I. The utility of immunohistochemistry
复制标题
DOI：
10.2353/jmoldx.2008.080031
复制
发表时间：
2008-07-01
影响因子：
4.1
通讯作者：
Shia, Jinru
中科院分区：
文献类型：
--
作者：
Shia, Jinru
免疫组化检测DNA错配修复（MMR）蛋白在筛查遗传性非息肉病性结直肠癌（HNPCC）综合征中的应用是近10年来研究的热点。特别关注的是免疫组化（IHC）与肿瘤微卫星不稳定性（MSI）测试的相对有用性。早期的工作集中在mutL同源物1（MLH1）和mutS同源物2（MSH2）已经造成了一个错误的印象，即在预测生殖系突变方面，IHC的灵敏度低于MSI检测。另一方面，最近的研究，包括减数分裂后分离增加2（PMS2）和MSH6，已经证明了IHC的预测价值，几乎等同于MSI检测。PMS2和MSH6的这种附加值可以通过MMR蛋白的生物学和生物化学性质来解释。在用PMS2和MSH6进行的IHC与MSI检测一样敏感的前提下，考虑到HIC容易获得并且通常便宜，并且重要的是，识别受影响的基因，将HIC视为比MSI检测更优化的一线筛选工具来识别HNPCC是合理的。MSI测试可以在模棱两可的情况下提供一个后备位置，同时仍然是一个重要的研究工具。然而，对于HIC作为一线筛查测试，病理学家和临床医生都需要意识到IHC结果可能被解释为“遗传信息”，并且应该建立适当的程序以确保患者的理解和同意。
The utility of immunohistochemical detection of DNA mismatch repair (MMR) protein in screening colorectal tumors for hereditary nonpolyposis colorectal cancer (HNPCC) syndrome has been the focus of much intensive research over the last 10 years. Particular attention has been given to the relative usefulness of immunohistochemistry (IHC) versus testing of tumor microsatellite instability (MSI). Earlier work that focused on mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) has created a false impression that IHC has a lower sensitivity than MSI testing in predicting germline mutation. More recent studies that included postmeiotic segregation increased 2 (PMS2) and MSH6, on the other hand, have demonstrated an IHC predictive value that is virtually equivalent to that of MSI testing. Such added value of PMS2 and MSH6 can be explained by the biological and biochemical properties of the MMR proteins. On the premise that IHC with PMS2 and MSH6 is as sensitive as MSI testing, given that HIC is easily available and generally inexpensive and, importantly, identifies the affected gene, it is reasonable to regard HIC as a more optimal first-line screening tool than MSI testing for identifying HNPCC. MSI testing can provide a fallback position in equivocal situations, while remaining an important research tool. However, for HIC to be used as a first-line screening test requires that both pathologists and clinicians be aware that IHC results may be construed as "genetic information," and that appropriate procedures should be established to ensure patient understanding and consent.