METHODS: 60 dMMR and 60 pMMR CRC samples identified by IHC were collected and their MSI status were detected using TrueMark™ MSI assay with an expanded panel of 13 markers. The overall performance and diagnostic concordance between TrueMark™ MSI test and MMR IHC analysis were assessed and analyzed.
RESULTS: According to the TrueMark™ test, 55 out of the 120 (45.8 %) CRCs were identified as MSI-high (MSI-H) with an instability at ≥ 4/13 markers. Compared with the MMR IHC analysis, an overall percent agreement of 94.2 % and a Kappa of 0.883 were achieved. For the seven inconsistent samples, tumor mutation burden analysis was performed and the results supported the diagnosis by TrueMark™ test. To confirm the robustness of the above findings, a validation was performed in an independent cohort comprising 51 consecutive CRCs. Furthermore, an optimized panel composed of NR-21, NR-24, NR-27, ABI-16, ABI-17 and ABI-20B was developed by multivariate logistic regression model, and showed 100 % agreement with the 13-marker panel for MSI detection in both the derivation and validation sets.
CONCLUSIONS: TrueMark™ MSI provides a fast, reliable and highly automated solution to MSI detection in Chinese CRC patients, and the new 6-marker panel we established shows promise deserving further evaluation.
方法:收集通过IHC鉴定的60dMMR和60pMMRCRC样品,并使用TrueMark™MSI测定用13个标记的扩展组检测它们的MSI状态。评估并分析了TrueMark™MSI测试和MMRIHC分析之间的总体性能和诊断一致性。
结果:根据TrueMark™测试,120个(45.8%)CRC中的55个被鉴定为MSI高(MSI-H),在≥4/13标记处不稳定。与MMRIHC分析相比,实现了94.2%的总体百分比一致性和0.883的Kappa。对于七个不一致的样本,进行了肿瘤突变负荷分析,结果支持TrueMark™检验诊断.此外,通过多元逻辑回归模型建立了由NR-21、NR-24、NR-27、ABI-16、ABI-17和ABI-20B组成的优化面板,并且在训练集和验证集中与用于MSI检测的13标记组显示100%的一致性。
结论:TrueMark™MSI提供了一种快速、可靠且高度自动化的中国CRC患者MSI检测解决方案,我们建立的新的6标记小组显示出值得进一步评估的希望。