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MSI-high means the tumour's DNA has unstable repeat sequences, the footprint of failed mismatch repair. It is measured by PCR or sequencing, gives the same answer as dMMR in most tumours, and unlocks the same immunotherapies.
Microsatellite instability is scored by PCR across a panel of mononucleotide repeats (MSI-H when a set fraction of markers is unstable, typically 2 of 5 Bethesda or Promega markers, or 30 percent or more of a larger panel) or by next-generation sequencing algorithms that count unstable loci across hundreds of sites; MSS is stable and MSI-L is intermediate and grouped with MSS. Labels write 'MSI-H or dMMR' and accept either route; FoundationOne CDx and Caris MI Cancer Seek carry MSI-H companion claims for pembrolizumab and dostarlimab, the Biocartis Idylla MSI test for nivolumab in colorectal cancer, and, in the other direction, the Promega OncoMate MSI and Caris assays report 'not MSI-H' to select pembrolizumab with lenvatinib in endometrial cancer.
In plain words · The four mismatch repair proteins proofread newly copied DNA; when a tumour loses one of them its DNA fills with small errors, and that state (dMMR or MSI-high) is what lets immunotherapy work across many cancers.
MSI-high on a PCR or sequencing report means the same for treatment as dMMR on a stain: checkpoint immunotherapy is on label across many cancers once other treatment has been tried, and first line in bowel cancer. A stable (MSS) result in endometrial cancer selects a different combination, pembrolizumab with lenvatinib. Either result should prompt a conversation about inherited risk.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
MSI-H: instability at the required fraction of tested microsatellite loci (for example 2 or more of 5 mononucleotide markers by PCR, or the sequencing panel's validated cut-off across many loci); otherwise microsatellite stable.
“Microsatellite instability – High (MSI-H)”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| MSI-H or dMMR, tumour-agnostic | Pembrolizumab | Metastatic cancer (cancer that has spread) | FDA | label |
| MSI-H or dMMR | Pembrolizumab | Colorectal cancer | FDA | label |
| MSI-H or dMMR (single agent after chemotherapy) | Nivolumab | Colorectal cancer | FDA | label |
| Not MSI-H / pMMR (selects the lenvatinib combination) | Lenvatinib | Endometrial cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| FoundationOne CDx | Foundation Medicine | Solid Tumors - Tissue | Pembrolizumab | P170019/S029 (02/18/2022) |
| MI Cancer Seek (MCS) | Caris Life Sciences | Solid Tumors - Tissue | Pembrolizumab | P240010 (11/05/2024) |
| MI Cancer Seek (MCS) | Caris Life Sciences | Solid Tumors - Tissue | Dostarlimab | P240010 (11/05/2024) |
| Idylla CDx MSI Test | Biocartis | Colorectal Cancer (CRC) - Tissue | NivolumabIpilimumab | P250005 (08/15/2025) |
| OncoMate MSI Dx Analysis System | Promega | Endometrial Carcinoma (EC) - Tissue | PembrolizumabLenvatinib | P240026 (11/05/2025) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
HER2 is as frequent in India as in the West, so HER2 testing pays off in the highest-incidence population, while tumour-agnostic immunotherapy markers will rarely apply. The paper also shows plasma testing is feasible where tissue is scarce.
For colon cancer that is mismatch-repair deficient (about 10-15% of colon cancers, more in older patients), a single short course of immunotherapy before surgery is now a reasonable standard and is far more effective than chemotherapy, which has little effect in this subtype. It requires testing every colon cancer for mismatch repair at diagnosis, before surgery. Whether some patients can safely skip surgery, as in dMMR rectal cancer, is the next question.
Cercek's dostarlimab study is the clearest demonstration that immunotherapy can replace surgery in a solid tumour: patients with dMMR rectal cancer can keep their rectum and avoid the permanent effects of pelvic radiotherapy and surgery. Non-operative management after PD-1 blockade is now in guidelines for this group, and MMR testing before treatment of rectal cancer is essential. The approach applies only to the 5-10% of rectal cancers that are dMMR.
The reference Western cohort for gallbladder cancer frequencies, deposited on cBioPortal as gbc_mskcc_2022, where the per-gene sample counts on OnCo were read. It supports panel testing at diagnosis: one patient in three has a targetable finding.
It tells the pathologist which pancreatic cancers to test for the one immunotherapy-responsive subgroup and how.
MSI testing has a very low yield in TNBC; TMB and PD-L1 are the immunotherapy biomarkers worth pursuing.
Every pancreatic cancer should be tested for mismatch repair deficiency because the 1 percent who have it can receive pembrolizumab, but responses in pancreatic cancer are less frequent and less durable than in other MSI-high cancers.
Every colorectal cancer should be tested for mismatch repair deficiency, because patients whose metastatic tumour is dMMR should receive pembrolizumab rather than chemotherapy as first treatment, gaining a much better chance of durable remission with fewer side effects. About a third of dMMR tumours do not respond initially, so early scans are essential and chemotherapy remains available. The trial does not apply to the 95% of metastatic colorectal cancers that are mismatch-repair proficient (the deficient share is higher in localised disease, about 15%).
Shares Mismatch repair deficiency and microsatellite instability in triple-negative breast cancer: a retrospective study of 440 patients, Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications, Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies, Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142).
Shares Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications, Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer, Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies, MSH2 loss in primary prostate cancer.
Shares Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies, Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Tumour-agnostic (tissue-agnostic) approval, Next-generation sequencing (NGS) and the tag biomarker.
Shares Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, FoundationOne CDx / Liquid CDx, Tumour-agnostic (tissue-agnostic) approval, Gallbladder cancer and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Next-generation sequencing (NGS), Endometrial cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Next-generation sequencing (NGS), Metastatic castration-resistant prostate cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Metastatic castration-resistant prostate cancer, Endometrial cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Tumour-agnostic (tissue-agnostic) approval, Metastatic cancer (cancer that has spread), Colorectal cancer and the tag biomarker.