Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China.
Department of Pathology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China; Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Pathol Res Pract. 2023 Apr;244:154390. doi: 10.1016/j.prp.2023.154390. Epub 2023 Feb 28.
Microsatellite instability (MSI) represents as a molecular hallmark of deficient MMR system at the genomic level. Increasing clinical significance of MSI status highlights the necessity of simple, accurate markers for detection. Although 2B3D NCI panel is the most widely applied, it has been questioned whether the performance of NCI panel is second to none in MSI detection.
We evaluated the efficacy of the NCI panel versus a 6-mononucleotide site panel (BAT25, BAT26, NR21, NR24, NR27, and MONO-27) in assessing MSI status of 468 Chinese patients with CRC, and compared MSI test results with the results by immunohistochemistry of four MMR proteins (MLH1, PMS2, MSH2, MSH6) in the present study. Clinicopathological variables were also collected, and their associations with MSI or MMR proteins status were analyzed using either the chi-square test or the Fisher's exact test.
MSI-H/dMMR was significantly associated with right colon involvement, poor differentiation, early stage, mucinous adenocarcinoma, negative lymph node, less neural invasion, and KRAS/NRAS/BRAF wild-type. As to the efficiency of detecting deficient MMR system, both panels had good concordance with MMR proteins expression by IHC, and 6-mononucleotide site panel outperformed NCI panel in sensitivity, specificity, positive predictive value, and negative predictive value numerically despite the lack of statistical significance. The advantage was more obvious in the sensitivity and specificity analyses of each single microsatellite markers from 6-mononucleotide site panel in comparison with NCI panel. Additionally, the rate of MSI-L detected by 6-mononucleotide site panel was much lower than that detected by the NCI panel (0.64% vs. 2.86%, P = 0.0326).
6-mononucleotide site panel had a greater ability to help resolve cases of MSI-L into either MSI-H or MSS. We propose that 6-mononucleotide site panel may be potentially more suitable than NCI panel for Chinese CRC population. Large-scale studies are warranted to validate our findings.
微卫星不稳定性（MSI）代表基因组水平上 MMR 系统缺陷的分子特征。MSI 状态的临床意义不断增加，凸显了对简单、准确的检测标志物的需求。虽然 2B3D NCI 面板是应用最广泛的，但人们质疑 NCI 面板在 MSI 检测中的性能是否是首屈一指的。
我们评估了 NCI 面板与 6 个单核苷酸位点面板（BAT25、BAT26、NR21、NR24、NR27 和 MONO-27）在评估 468 例中国 CRC 患者 MSI 状态中的疗效，并将 MSI 检测结果与本研究中四种 MMR 蛋白（MLH1、PMS2、MSH2、MSH6）的免疫组化结果进行比较。还收集了临床病理变量，并使用卡方检验或 Fisher 精确检验分析它们与 MSI 或 MMR 蛋白状态的关系。
MSI-H/dMMR 与右半结肠癌、低分化、早期、黏液腺癌、阴性淋巴结、较少神经浸润和 KRAS/NRAS/BRAF 野生型显著相关。至于检测缺陷 MMR 系统的效率，两个面板与免疫组化中 MMR 蛋白的表达均具有良好的一致性，尽管缺乏统计学意义，但 6 个单核苷酸位点面板在敏感性、特异性、阳性预测值和阴性预测值方面均优于 NCI 面板。与 NCI 面板相比，6 个单核苷酸位点面板中每个单个微卫星标记的敏感性和特异性分析中优势更为明显。此外，6 个单核苷酸位点面板检测到的 MSI-L 率远低于 NCI 面板（0.64%比 2.86%，P=0.0326）。
6 个单核苷酸位点面板更有助于将 MSI-L 病例分为 MSI-H 或 MSS。我们提出，6 个单核苷酸位点面板可能比 NCI 面板更适合中国 CRC 人群。需要进行大规模研究来验证我们的发现。
