Abstract：
BACKGROUND: Microsatellite instability (MSI) and mismatch repair (MMR) detection is valuable in assessing prognosis and treatment options. However, the conventional detection methods such as immunohistochemistry (IHC) are limited by not fully consistent results as well as a long turnaround time. TrueMark™ MSI Assay is a novel solution for MSI analysis, but lack of research support in the Chinese colorectal cancer (CRC) patients.
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.
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.
摘要：
背景：微卫星不稳定性（MSI）和错配修复（MMR）检测在评估预后和治疗选择方面很有价值。然而,常规检测方法如免疫组织化学(IHC)受限于结果不完全一致以及较长的周转时间.TrueMark™MSI分析是一种新型的MSI分析解决方案，但缺乏对中国结直肠癌(CRC)患者的研究支持。
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。
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。
