biomarkersBiomarker

MSI-high (microsatellite instability by PCR or sequencing)

aka MSI-H, MSI-high, MSI high, microsatellite instability-high, microsatellite unstable, MSI status, MSI-H/dMMR, MSS, microsatellite stable

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.

Part ofMismatch repair proteins (MLH1, MSH2, MSH6, PMS2)· MLH1, MSH2, MSH6, PMS2Other readoutsdMMR All readouts

Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2): what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

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 status 4 approval thresholds

What it means for a patient

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.

Scoring rule

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

Thresholds used in approvals

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

Drugs whose label names it

Pembrolizumab Nivolumab Lenvatinib

Companion diagnostics (FDA list)

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	Nivolumab Ipilimumab	P250005 (08/15/2025)
OncoMate MSI Dx Analysis System	Promega	Endometrial Carcinoma (EC) - Tissue	Pembrolizumab Lenvatinib	P240026 (11/05/2025)

Tests that measure it

FoundationOne CDx MSI by PCR (Promega MSI Analysis System and equivalents)BostonGene Tumor Portrait Tempus xT and xT CDx FoundationOne CDx FoundationOne Liquid CDx Caris MI Cancer Seek StrataNGS Illumina TruSight Oncology 500 Natera Altera Exact Sciences OncoExTra Labcorp OmniSeq INSIGHT

Trials that name this readout

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.