Molecular Pathology and Therapeutic Targets Group, Hospital La Paz Institute for Health Research (IdiPAZ), 28046, Madrid, Spain; Center for Biomedical Research in the Cancer Network (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain.
Center for Biomedical Research in the Cancer Network (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain; Translational Oncology Research Laboratory, Hospital La Paz Institute for Health Research (IdiPAZ), 28046, Madrid, Spain.
Mol Cell Probes. 2024 Oct;77:101976. doi: 10.1016/j.mcp.2024.101976. Epub 2024 Jul 31.
DNA mismatch repair (MMR) deficiency (dMMR) testing is now recommended in endometrial cancer. Defect identification in the molecules participating in this pathway, or the presence of microsatellite instability, are commonly employed for this purpose. Novel methods are continuously evolving to report dMMR/microsatellite instability and to easily perform routine diagnoses.
The main aim of this study was to compare the concordance of the Idylla microsatellite instability test for the identification of dMMR endometrial cancer samples defined by immunohistochemistry and MMR genomic status.
We applied the Idylla MSI test to 126 early-stage endometrial cancer cases with MMR testing by immunohistochemistry and genomic characterization (methylation in MLH1 and sequence alterations in MLH1, PMS2, MSH2 and MSH6). Individual markers and overall specific performance indicators were explored.
The Idylla platform achieved a higher global concordance rate with MMR genomic status than with immunohistochemistry (75 % and 66 %, respectively). Sensitivity and specificity are also higher (75 % vs 66 % and 96 % vs 90 %, respectively). Clustering analysis split the patients into 2 well-differentiated clusters, the pMMR and the dMMR group, represented by MLH1/PMS2 loss and the MLH1 methylated promoter. Overall, immunohistochemistry and MMR genomic status identified more dMMR cases than did the Idylla test, although correlations were improved with a modified Idylla test cut-off.
Performance of the Idylla test was better correlated with MMR genomic status than MMR immunohistochemistry status, which improved with a modified test cut-off. Further studies are needed to confirm the cut-off accuracy.
DNA 错配修复（MMR）缺陷（dMMR）检测现在被推荐用于子宫内膜癌。通常采用识别参与该途径的分子缺陷或微卫星不稳定性的方法来进行此检测。目前不断有新的方法用于报告 dMMR/微卫星不稳定性并方便进行常规诊断。
本研究的主要目的是比较免疫组化检测定义的 dMMR 子宫内膜癌样本与 Idylla 微卫星不稳定性检测在识别 dMMR 方面的一致性，以及与 MMR 基因组状态的一致性。
我们对 126 例早期子宫内膜癌病例进行了 Idylla MSI 检测，这些病例的 MMR 检测采用免疫组化和基因组特征分析（MLH1 甲基化和 MLH1、PMS2、MSH2 和 MSH6 序列改变）。探索了个体标志物和整体特异性表现指标。
Idylla 平台与 MMR 基因组状态的总体一致性比免疫组化更高（分别为 75%和 66%）。灵敏度和特异性也更高（分别为 75%比 66%和 96%比 90%）。聚类分析将患者分为 2 个分化良好的组，即 pMMR 和 dMMR 组，分别代表 MLH1/PMS2 缺失和 MLH1 甲基化启动子。总的来说，免疫组化和 MMR 基因组状态比 Idylla 检测识别出更多的 dMMR 病例，尽管通过修改后的 Idylla 检测截止值，相关性得到了改善。
Idylla 检测的性能与 MMR 基因组状态的相关性优于与 MMR 免疫组化状态的相关性，通过修改后的检测截止值可以提高相关性。需要进一步的研究来确认截止值的准确性。
