The end result of MSI standardized testing: 4 major guidelines/consensus updated from 2021, talk about the site selection of MSI testing

As we all know, in the process of standardized detection of microsatellite instability (MSI), the selection of detection sites is very important.

Because MSI is to detect the status of microsatellites, and humans have 19 million microsatellite sites, it is more difficult to detect more sites selected, and fewer sites are not representative.

Internationally, the choice of MSI sites has actually been determined as early as 30 years ago.
In the process of 30 years, although "new people" have appeared in large numbers, the final representative sites have never changed—that is, The 5-site detection panel (PCR + capillary electrophoresis) includes two sets of sites, one is NCI's 2B3D Panel (BAT-25, BAT-26, D5S346, D17S250, D2S123), and the other 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 testing kit, MSI testing has recently become a hot spot of clinical concern.

However, although the standardized detection of MSI has quietly arrived, the importance of MSI site selection is still being ignored.
There are still panels on the market that have no consensus recommendations and lack of clinical data to confuse people.

Since the selection of MSI detection sites is biased, it will directly affect the detection rate of patients with microsatellite highly unstable (MSI-H).
The wrong selection will greatly increase the missed diagnosis rate, which involves the lives of thousands of tumor patients.

In April, domestic and foreign colorectal cancer and gastric cancer intensively released updated guidelines.
Let us look at the site selection in the standardized MSI detection from the guidelines! "NCCN Gastric Cancer Guidelines (V1 Version 2021)" The first guide is the 2021 "NCCN Gastric Cancer Guidelines (V1 Version)".The selection of MSI sites in the gastric cancer guidelines is very clear.
For the 5-site Panel (2B3D NCI Panel and 5-Single Nucleotide Panel), 6 or more MSI panels are not recommended.

The second guideline of "NCCN Colorectal Cancer Guidelines (Version 2021 V2)" is the "NCCN Colorectal Cancer Guidelines (V2)" in 2021: First, refer to the "NCCN Genetic and Family Risk Assessment Guidelines for the recommendation of MSI detection sites" ".

In the "NCCN Genetic and Family Risk Assessment Guidelines", consistent with the "NCCN Gastric Cancer Guidelines (2021 V1 Edition)", only 2B3D NCI Panel and 5 single-nucleotide Panels are recommended.

The third part of the "Expert Consensus on High-throughput Sequencing for Molecular Detection of Colorectal Cancer" is the latest 2021 "Expert Consensus on High-throughput Sequencing for Molecular Detection of Colorectal Cancer".
The site recommendation for MSI detection is very clear, and NCI is recommended.
The recommended 2B3D site, and pointed out that "in clinical applications, it is recommended to use the NMPA approved MSI kit".

The fourth guideline of "CSCO Colorectal Cancer Diagnosis and Treatment Guidelines (2021 Edition)" is the "CSCO Colorectal Cancer Diagnosis and Treatment Guidelines (2021 Edition)" that was updated in Beijing on April 24.

From the four latest editions 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 Promega Panel of 5 single nucleotides.

The reason why the current clinical work continues to emphasize the selection of MSI detection sites is that it will greatly affect the detection rate of MSI, and the wrong site selection will lead to missed diagnosis of MSI-H patients.
This is also supported by data.

The 2B3D site of NCI was finally confirmed by screening more than 30 microsatellite sites through two important multi-center studies in 1997.
Therefore, almost all foreign guidelines are based on these two studies recommending MSI detection sites in the year.
. In the Chinese population, Zhang et al.
's Meta-analysis data including nearly 6000 cases of MSI test results finally showed that the detection rate of 2B3D locus and Promega Panel is consistent in sporadic colorectal cancer (13.
5% vs 12.
9%), but If other single-nucleotide panels (6-site MSI Panel) are used, the detection rate is only 7.
7%! At least 30% of MSI-H tumor patients have been missed! Many clinicians believe that the incidence of MSI in China is low, and its detection rate is even lower than that of MMR protein immunohistochemistry.
A large part of the reason is that the previous domestic MSI unlicensed kit site selection was wrong.
.

Zhang et al.
, JGO, 2020 summarized more than 30 global guidelines/consensus on MSI and large-scale immunosuppressive clinical studies at home and abroad, and most of them recommend 5-site Panel (2B3D site and Promega) Currently, there is only one consensus recommendation for Panels with 6 to 7 sites.

Therefore, for clinical or pathology teachers, the site selection of MSI detection is actually very clear.
In order to reduce missed diagnosis, in order for every MSI-H patient to be diagnosed and hope for a living, follow the clinical data.
Follow the guidelines and recommendations, and use the most standardized method to detect MSI!