A comparison of performance of 6-mononucleotide site panel and NCI panel for microsatellite instability detection in patients with colorectal adenocarcinoma

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.