Wang Yang, Shi Chanjuan, Eisenberg Rosana, Vnencak-Jones Cindy L
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
J Mol Diagn. 2017 Jan;19(1):57-64. doi: 10.1016/j.jmoldx.2016.07.008. Epub 2016 Nov 1.
Colorectal (CRCs) and endometrioid (EMCs) cancers in patients with Lynch syndrome exhibit microsatellite instability (MSI) detected by PCR or immunohistochemistry (IHC). While both assays are equally sensitive for CRCs, some suggest that PCR has a higher false-negative rate than IHC in EMCs. We assessed the MSI profiles of 91 EMC and 311 CRC specimens using five mononucleotide repeat markers: BAT25, BAT26, NR21, NR24, and MONO27. EMCs with high MSI (MSI-H) showed a mean left shift of 3 nucleotides (nt), which was significantly different from 6 nt in CRCs. A shift of 1 nt was observed in multiple markers in 76% of MSI-H EMCs, whereas only 12% of MSI-H CRCs displayed a 1-nt shift in one of five markers. IHC against four mismatch repair proteins was performed in 78 EMCs. Loss of staining in one or more proteins was detected in 18 of 19 tumors that were MSI-H by PCR. When EMC tumor cell burden was diluted to <30%, MSI-H was no longer observed in two of three EMCs with a mean nucleotide shift of 1 nt. These results indicate that EMC and CRC MSI profiles are different and that caution should be exercised when interpreting the results, as subtle, 1-nt changes may be missed. These findings provide a potential cause of previously reported discordant MSI and IHC results in EMCs.
林奇综合征患者的结直肠癌（CRCs）和子宫内膜样癌（EMCs）通过聚合酶链反应（PCR）或免疫组织化学（IHC）检测显示微卫星不稳定性（MSI）。虽然这两种检测方法对CRCs的敏感性相同，但一些研究表明，在EMCs中，PCR的假阴性率高于IHC。我们使用五个单核苷酸重复标记：BAT25、BAT26、NR21、NR24和MONO27评估了91例EMC和311例CRC标本的MSI谱。高微卫星不稳定性（MSI-H）的EMCs平均向左移位3个核苷酸（nt），这与CRCs的6 nt显著不同。在76%的MSI-H EMCs中，多个标记观察到1 nt的移位，而只有12%的MSI-H CRCs在五个标记之一中显示1 nt的移位。对78例EMCs进行了针对四种错配修复蛋白的免疫组织化学检测。在通过PCR检测为MSI-H的19个肿瘤中的18个中检测到一种或多种蛋白的染色缺失。当EMC肿瘤细胞负荷稀释至<30%时，三个平均核苷酸移位为1 nt的EMCs中有两个不再观察到MSI-H。这些结果表明，EMC和CRC的MSI谱不同，在解释结果时应谨慎，因为可能会遗漏细微的1 nt变化。这些发现为先前报道的EMCs中MSI和IHC结果不一致提供了一个潜在原因。
