Departments of Pathology and Molecular Genetics, Hospital U Arnau de Vilanova and Hospital U de Bellvitge, University of Lleida, IRBLLEIDA, IDIBELL, CIBERONC, Av. Alcalde Rovira Roure, 80 25198, Lleida, Spain.
Department of Pathology, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey.
Virchows Arch. 2021 May;478(5):851-863. doi: 10.1007/s00428-020-02962-x. Epub 2020 Nov 10.
Microsatellite instability (MSI) is present in 15-20% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla™ MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla™ testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla™ results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla™ MSI Assay were equally distributed over the seven biomarkers, and 84.48% of the MSI-high samples had ≥ 5 mutated biomarkers, while 98.25% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla™ MSI Assay and immunohistochemistry was 96.39% (988/1025); 17/37 discordant samples were found to be concordant when a third method was used. Compared with routine molecular methods, the concordance level was 98.01% (789/805); third-method analysis found concordance for 8/16 discordant samples. The failure rate of the Idylla™ MSI Assay (0.23%; 3/1301) was lower than that of referenced immunohistochemistry (4.37%; 47/1075) or molecular assays (0.86%; 7/812). In conclusion, lower failure rates and high concordance levels were found between the Idylla™ MSI Assay and routine tests.
微卫星不稳定性（MSI）存在于 15-20%的原发性结直肠癌中。评估 MSI 状态是为了检测林奇综合征，指导辅助化疗，确定预后，并作为检查点阻断抑制剂的伴随测试。传统上，MSI 状态是通过免疫组织化学或分子方法来确定的。Idylla™ MSI 分析是一种全自动的分子方法（包括自动结果解释），使用七种新的 MSI 生物标志物（ACVR2A、BTBD7、DIDO1、MRE11、RYR3、SEC31A 和 SULF2），不需要匹配的正常组织。在这项真实世界的全球研究中，44 个临床中心对总共 1301 个存档的结直肠癌福尔马林固定石蜡包埋（FFPE）组织切片进行了 Idylla™ 检测，并将 Idylla™ 结果与这些地点常规诊断检测的可用结果进行了比较。Idylla™ MSI 分析检测到的 MSI 突变在这七个生物标志物中分布均匀，84.48%的 MSI 高样本有≥5 个突变的生物标志物，而 98.25%的微卫星稳定样本有 0 个突变的生物标志物。Idylla™ MSI 分析与免疫组织化学之间的一致性水平为 96.39%（988/1025）；当使用第三种方法时，17/37 个不一致的样本被发现是一致的。与常规分子方法相比，一致性水平为 98.01%（789/805）；第三种方法分析发现 8/16 个不一致的样本是一致的。Idylla™ MSI 分析的失败率（0.23%；3/1301）低于参考免疫组织化学（4.37%；47/1075）或分子分析（0.86%；7/812）。总之，Idylla™ MSI 分析与常规检测之间的失败率较低，一致性水平较高。
