In recent years, in step with advancements in diagnosis and treatment and the emergence of targeted drugs and immunotherapy, immune checkpoint inhibitors have become more and more widely used. Microsatellite Instability Testing For Tumors Diagnosis (MSI) is an important biomarker in predicting the response of patients to immune checkpoint inhibitors, and is also a pan-cancer biomarker, which plays an important role in the diagnosis and treatment of tumors.

 

What is MSI?

Microsatellite Instability (MSI) refers to the phenomenon of microsatellite (MS) sequence length variation caused by insertion or deletion during DNA replication, often caused by Mismatch Repair (MMR) defects. MS sequences, which are short and repetitive DNA sequences, generally consist of 1 to 6 nucleotides and are arranged in tandem repeats, among which the common types are two-base CA/GA/GT or single-base A/T.

 

MSI detection method

	MMR-IHC	MSI-PCR-CE	MSI-NGS
Detection content	·MMR protein expression (MLH-1, MSH-2, MSH-6, PMS-2)	·Single-base/Two-base microsatellite sequence length variation	·Repeat sequence length variation at satellite loci, varying in the number of microsatellite loci for different panels
evaluation criteria	·If any one of the four (4) MMR proteins is missing, it is considered dMMR	·≥ 2 sites destabilized as MSI-H (5 – 6 sites detected)	·Threshold based on different sites and analytical methods
Advantages	·Mature method, Wide clinical application ·Low price ·Direct indication of MMR protein deficiency	·Gold standard ·Accurate, simple and fast ·High sensitivity and specificity ·Easy standardization and automation	·Mostly used for accompanying testing of medium and large panels with low totalcosts ·ata analysis. optimized in conjunction with the bioinformation algorithm can greatly improve the detectable rateof samples with low
Disadvantages	·Requires standardized tissue pretreatment ·Tissue heterogeneity ·Presence of false-negative and false-positive results ·Highly depends on the experience of pathologists, which inevitably introduce bias.	·Moderate price	·Complicated technique and difficult to be standardized. ·Lack of industry uniform standards and extensive validation, which may result in inconsistent output due to different algorithms ·High price ·No certified reagents
Clinical applications	·The current basic recommendation for clinical MSI/MMR testing in China	·Recognized gold standard for MSI testing, recommended in laboratories with molecular diagnostics facilities	·Detection of MSI alone is slightly longer in turn around time. ·Quality of probe design and bioinformation algorithms within the market vary, and the cost of screening and validation is high

 

Clinical significance of MSI

Screening for Lynch syndrome

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant inherited tumor with a familial predisposition, caused by germline mutations in the MMR gene. Lynch syndrome accounts for about 3% to 5% of all patients with colorectal carcinoma (CRC), and the vast majority of patients with Lynch syndrome present with the phenotype of MSI-H. MSI can therefore be used as a general screening tool for Lynch syndrome.

 

MSI is a prognostic factor in stage II colorectal cancer

At present, postoperative adjuvant chemotherapy is recommended for high-risk stage II CRC patients in clinical practice. For CRC patients with dMMR/MSI-H phenotype, although histological differentiation is often poor, the prognosis is usually good. Therefore, dMMR/MSI test can determine the efficacy of adjuvant chemotherapy for high-risk stage II CRC patients with poor histological differentiation.

 

MSI is a predictor of response to adjuvant chemotherapy for stage II colorectal cancer

A meta-analysis showed that patients with stage II/III CRC with the dMMR/MSI-H phenotype did not benefit from adjuvant chemotherapy using single-agent 5-FU, and patients with stage II dMMR/MSI-H conversely experienced shorter survival with adjuvant chemotherapy using single-agent 5-FU (HR = 2.95; 95% CI: 1.02 to 8.54) . Data suggests that adjuvant chemotherapy using single-agent 5-FU alone for stage II CRC patients with the dMMR/MSI-H phenotype, instead of achieving a survival benefit, adversely impacts long-term survival.

 

MSI is a predictor of response to immunotherapy efficacy in advanced solid tumors

Patients with advanced solid tumors of the MSI-H phenotype tend to experience significant efficacy when treated with immune checkpoint inhibitors such as programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibodies. Therefore, as a predictive biomarker of immunotherapy efficacy in patients with advanced/metastatic solid tumors, especially CRC patients, MSI detection can provide important guidance for clinical treatment.

 

 

Dynegene MSI testing products

Dynegene has independently developed 746 gene panel related to pan-solid tumors, among which applicable sample types included cfDNA, tissue samples, and FFPE, with high sensitivity, suitable for NGS tumor liquid biopsy. The testing products cover a variety of drug options, including anti-tumor targeted drugs approved by the FDA and NMPA for marketing, immunotherapeutic drugs and target genes for some drugs under development. The scope of detection includes regions such as coding regions, intronic regions, and promoter regions to provide a comprehensive tumor map and completely assess MSI and TMB abnormalities associated with immunotherapy.

Product Name	Item No.	Sample Requirements	Target Size	Unique double-stranded RNA probes capture with	Advantages
QuarXeq Pan-Cancer Ultra Panel	NY1015	10 ng - 200 ng. Suitable for FFPE samples	5.9Mb	high coverage and complete retained library information	Comprehensive tumor mapping and complete assessment of MSI and TMB