It is well known that the choice of detection site is crucial in the normalization detection of microsatellite instability (MSI). Because MSI is the state of detecting microsatellites, and humans have 19 million microsatellite loci, it is more difficult to detect if there are too many loci selected, and if there are fewer loci selected, it is not representative.
Internationally, the selection of MSI loci has actually been finalized as early as 30 years ago. In the process of 30 years, although "new people" have been tinkering, the final representative locus has never changed - that It is a 5-site detection Panel (PCR+capillary electrophoresis), including two sets of sites, one set is NCI's 2B3D Panel (BAT-25, BAT-26, D5S346, D17S250, D2S123), and the other set is 5 Single nucleotide Panel (usually refers to Promega: BAT-25, BAT-26, NR-21, NR-24, MONO-27).
In China, with the approval of the first MSI detection kit, MSI detection has become a hot spot of clinical recently. However, although the standardized detection of MSI has come quietly, the importance of MSI site selection is still being ignored, and there are still panels on the market without consensus recommendations and lack of clinical data confirmation.
If there is a deviation in the selection of MSI detection sites, it will directly affect the detection rate of patients with microsatellite highly unstable (MSI-H), and the wrong selection will greatly increase the missed diagnosis rate, which involves the lives of millions of tumor patients. . In April, colorectal cancer and gastric cancer at home and abroad intensively released updated guidelines, let us look at the site selection in the standardized detection of MSI from the guidelines!
"NCCN Guidelines for Gastric Cancer (2021 V1)"
The first guideline is the 2021 "NCCN Guidelines for Gastric Cancer (V1)".The selection of MSI sites in the gastric cancer guideline is very clear. Panels with 5 sites (NCI Panel of 2B3D and Panel of 5 single nucleotides) do not recommend panels with 6 or more MSI detection panels.
"NCCN Guidelines for Colorectal Cancer (2021 V2)"
The second guideline is the 2021 "NCCN Guidelines for Colorectal Cancer (V2)": First, the recommendation on MSI testing sites is referred to "NCCN Genetic and Family Risks" Evaluation Guide.
In the "NCCN Genetic and Family Risk Assessment Guidelines", which is consistent with the "NCCN Guidelines for Gastric Cancer (2021 V1)", only the 2B3D NCI Panel and 5 single-nucleotide panels are recommended.
"Expert Consensus on High-throughput Sequencing for Molecular Detection of Colorectal Cancer"
The third edition is the latest "Expert Consensus on High-throughput Sequencing for Molecular Detection of Colorectal Cancer" in 2021, in which the site recommendation for MSI detection is very clear. The 2B3D locus recommended by NCI was adopted, and it was pointed out that "the NMPA-approved MSI kit is recommended for clinical application".
"CSCO Colorectal Cancer Diagnosis and Treatment Guidelines (2021 Edition)"
The fourth guideline is the "CSCO Colorectal Cancer Diagnosis and Treatment Guidelines (2021 Edition)" just updated on April 24 in Beijing .
From the 4 latest versions of the guidelines/consensus above, we can see that the current gold standard method for MSI detection is PCR + capillary electrophoresis, and there are only two site selections, one is NCI's 2B3D Panel, and the other is 5 single nucleotide panels from Promega. The reason why
is constantly emphasizing the selection of MSI detection sites in clinical work is that this will greatly affect the detection rate of MSI, and the wrong site selection will lead to the missed diagnosis of in MSI-H patients, which is also supported by data. .The 2B3D locus of
NCI was finally confirmed by screening more than 30 microsatellite loci in two important multi-center studies in 1997, so almost all foreign guidelines recommend MSI detection loci based on these two studies in that year. .
In the Chinese population, Zhang et al. included Meta-analysis data of nearly 6000 MSI test results and finally showed that the positive rate of the 2B3D locus and the Promega Panel was the same in sporadic colorectal cancer (13.5% vs 12.9%). ), but if other single-nucleotide Panels (MSI Panels with 6 sites) are used, the positive rate of detection is only 7.7%! At least 30% of patients with MSI-H tumors are missed!
Before
, many clinicians believed that the incidence of MSI in China was low, and even the detection rate was lower than that of MMR protein immunohistochemistry. To.
Zhang et al., JGO, 2020
Summary
Looking at more than 30 guidelines/consensus about MSI worldwide and large-scale immunosuppressive clinical studies at home and abroad, the vast majority recommend 5-site Panel (2B3D site). and Promega), currently there is only one consensus recommending Panel with 6-7 loci. Therefore, for teachers in clinical or pathology departments, the site selection of MSI to detect is actually very clear. In order to reduce missed diagnosis, in order that every MSI-H patient can be diagnosed and have the hope of life, follow Clinical data, follow the guideline recommendations, and use the most standardized method to detect MSI!
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