Gastroenterology Department, Poitiers University Hospital, Poitiers, France.
Faculty of Medicine, University of Poitiers, Poitiers, France; INSERM 1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, Poitiers, France; Cancer Biology Department, Poitiers University Hospital, Poitiers, France.
ESMO Open. 2021 Jun;6(3):100120. doi: 10.1016/j.esmoop.2021.100120. Epub 2021 Apr 28.
DNA mismatch repair system deficiency (dMMR) is found in 15% of colorectal cancers (CRCs). Two methods are used to determine dMMR, immunohistochemistry (IHC) of MMR proteins and molecular testing of microsatellite instability (MSI). Only studies with a low number of patients have reported rates of discordance between these two methods, ranging from 1% to 10%.
Overall, 3228 consecutive patients with CRCs from two centers were included. Molecular testing was carried out using the Pentaplex panel and IHC evaluated four (MLH1, MSH2, MSH6, and PMS2; cohort 1; n = 1085) or two MMR proteins (MLH1 and MSH2; cohort 2; n = 2143). The primary endpoint was the rate of discordance between MSI and MMR IHC tests.
Fifty-one discordant cases (1.6%) were initially observed. Twenty-nine out of 51 discordant cases were related to IHC misclassifications. In cohort 1, after re-reading IHC and/or carrying out new IHC, 16 discordant cases were reclassified as nondiscordant. In cohort 2, after the addition of MSH6/PMS2 IHC and re-examination, 13 were reclassified as nondiscordant. In addition, 10 misclassifications of molecular tests were identified. Finally, only 12 discordant cases (0.4%) remained: 5 were proficient MMR/MSI and 7 were dMMR/microsatellite stable.
Our study confirmed the high degree of concordance between MSI and MMR IHC tests. Discordant cases must be reviewed, and if needed, tests must be repeated and analyzed by an expert team.
DNA 错配修复系统缺陷（dMMR）存在于 15%的结直肠癌（CRC）中。有两种方法可用于确定 dMMR，即 MMR 蛋白的免疫组织化学（IHC）和微卫星不稳定性（MSI）的分子检测。只有少数患者的研究报告了这两种方法之间的不一致率，范围为 1%至 10%。
共有来自两个中心的 3228 例连续 CRC 患者纳入研究。使用 Pentaplex 面板进行分子检测，免疫组化评估四个（MLH1、MSH2、MSH6 和 PMS2；队列 1；n=1085）或两个 MMR 蛋白（MLH1 和 MSH2；队列 2；n=2143）。主要终点是 MSI 和 MMR IHC 检测之间的不一致率。
最初观察到 51 例不一致病例（1.6%）。51 例不一致病例中有 29 例与 IHC 分类错误有关。在队列 1 中，在重新阅读 IHC 和/或进行新的 IHC 后，16 例不一致病例被重新分类为无不一致。在队列 2 中，在添加 MSH6/PMS2 IHC 并重新检查后，13 例被重新分类为无不一致。此外，还发现了 10 例分子检测的错误分类。最后，只有 12 例不一致病例（0.4%）仍然存在：5 例为 MMR/MSI 功能正常，7 例为 dMMR/微卫星稳定。
本研究证实了 MSI 和 MMR IHC 检测之间具有高度一致性。必须对不一致病例进行审查，如果需要，必须重复检测并由专家组进行分析。
