What is Microsatellite Instability?
Discover how instability in DNA sequences helps guide treatment and improve cancer care.
MSI Made Simple
Microsatellite instability, or MSI, happens when the body’s DNA repair system — called mismatch repair (MMR) — doesn’t work properly. This allows small, repeating sections of DNA (called microsatellites) to change when they shouldn’t.
When this repair system fails, DNA errors build up. Over time, this can lead to genetic instability ultimately triggering carcinogenesis.
MSI is found in several types of cancer, especially:
– Colorectal cancer
– Endometrial (uterine) cancer
– Gastric (stomach) cancer
– 30+ other cancer types
Knowing whether a tumor has MSI can help doctors:
– Diagnose certain cancers
– Predict how aggressive the cancer may be
– Choose the right treatment — some MSI-positive tumors respond better to immunotherapy
Why MSI Matters In Cancer?
🧪 Hereitary Cancer Fingerprint
Compatible with Whole-Exome or Targeted Panels, from FASTQ/BAM.
📈 Prognosis Impact
MSI-High tumors often respond better to certain therapies
💉 Theranostic biomarkers
Predicts effectiveness of immunotherapy
However, not all MSI-H/dMMR tumors respond to immune checkpoint inhibitors (ICI) and — beyond MSI-H/dMMR status — predictive biomarkers for sensitivity of these tumors to ICIs are lacking; genomic and transcriptomic signatures might help refine patient selection, but require further validation.
In early-stage MSI-H/dMMR cancers, ICIs show promising efficacy in the neoadjuvant setting, potentially enabling non-surgical, organ-preserving approaches and improved outcomes.
MSI In Cancer: The Clinical View
Traditional vs Genomic Testing Methods
Analytical methods
Advantages
Limitations
Turn around time
Immunohistochemistry (IHC)
Identify only the loss of expression of MMR proteins
– Cost-effective
– Simple workflow
– Widespread technology
– Applicable to any cancer type
– False negative results occurrence
– Limited evolutivity, unstandardized
– Tissue only
1 day/sample
PCR-based methods
Detect a few appropriate microsatellite markers
– Gold standard in colorectal cancer
– Cost-effective
– Technology not very scalable and long processing time
– Consumes tumor material
– Low performance outside colorectal cancers
1 week/sample
NGS-based methods
Detect mutations in microsatellite sequences of tumor DNA
– High-throughput technology
– Better sensitivity with high growth potential (pan-cancer, liquid biopsy)
– Coupling MSI analysis with the determination of hot spot mutations and other complex molecular signatures
– Longer turnaround time
– No available standard
– Unreliable FDA-approved MSI sensor te
2 weeks for a 96 samples sequencing batch (i.e. in average 0.1 days/sample)
What Experts Are Saying
Challenges In MSI Testing Today
🧪 Outdated Methods
PCR and IHC tests can miss MSI cases or give inconclusive results — especially in low-quality or rare tumor samples.
🔬 Lack of Standardization
Labs use different panels and thresholds, leading to inconsistent results and limited comparison across institutions.
💻 Limited Access to NGS
NGS-based MSI detection is underused, despite being more accurate, scalable, and compatible with tumor-only data and liquid biopsies.
