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The 'normal' result on the mismatch-repair test: the tumour has intact DNA spell-checking and few mutations. It describes about 95% of metastatic colorectal cancers and means checkpoint inhibitors alone are unlikely to work.
The opposite of MSI-high/dMMR. MSS tumours have low mutational burden and few neoantigens, so PD-1 blockade produced almost no responses in colorectal cancer (KEYNOTE-016), and the immunotherapy revolution in dMMR colorectal and endometrial cancer (CheckMate 8HW, dostarlimab) has bypassed them. Making MSS colorectal cancer immune-responsive with combinations (botensilimab-balstilimab, KRAS inhibitors plus PD-1, cancer vaccines) is one of the field's biggest open problems. In endometrial cancer pMMR patients benefit less from adding immunotherapy to chemotherapy but still gain (RUBY, NRG-GY018).
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
The first credible response signal in microsatellite stable colorectal cancer, and the reason the field's attention has moved to Fc engineering and to excluding patients with active liver metastases, in whom responses are rare.
It is the definitive negative result for unselected checkpoint blockade in microsatellite-stable colorectal cancer, and the reason later attempts have moved to Fc-enhanced CTLA-4 antibodies, TGF-beta blockade and vaccines rather than PD-L1 plus MEK.
It is the clearest mechanistic answer to why microsatellite-stable colorectal cancer resists immunotherapy, and the rationale for every TGF-beta plus checkpoint combination now in trials in this disease.
It defines a small group with an excellent prognosis that no repair immunohistochemistry panel or MSI assay will find, and it is the main argument for sequencing rather than staining alone in younger patients.
This small trial explained why colorectal cancer had seemed immune-resistant (most is MMR-proficient) and established the principle that a genomic feature, not the tissue of origin, can predict immunotherapy response. It led directly to the 2017 tissue-agnostic approval of pembrolizumab and to routine MMR/MSI testing of many cancers. Every patient with advanced dMMR cancer should now be considered for checkpoint blockade.
It made TGF-beta the central target of the microsatellite-stable half of the disease, which is the line that leads to Tauriello's immune-evasion work and to the TGF-beta plus checkpoint combinations in trials.
It fixes the metastatic prevalence figures every subsequent trial design has used, and it separates two biomarkers that travel together: BRAF, not mismatch repair deficiency, is what makes the prognosis bad.
It is the reason the immunotherapy-eligible fraction of metastatic colorectal cancer is about 5% rather than the 15% quoted for resected disease, and it frames microsatellite instability as a barrier to metastasis that becomes a liability once crossed.
Shares VENTANA MMR RxDx Panel, MSI and mismatch-repair testing, MSI-high (microsatellite instability by PCR or sequencing), Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma.
Shares CheckMate 8HW, MSI and mismatch-repair testing, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, MSI-high (microsatellite instability by PCR or sequencing).
Shares Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer, POLE, Advanced or recurrent endometrial cancer, Tumour mutational burden (TMB).
Shares CheckMate 8HW, MSI and mismatch-repair testing, MSI-high (microsatellite instability by PCR or sequencing), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2).
Shares MSI and mismatch-repair testing, MSI-high (microsatellite instability by PCR or sequencing), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial, CheckMate 8HW, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Hot vs cold tumours.
Shares VENTANA MMR RxDx Panel, MSI and mismatch-repair testing, MSI-high (microsatellite instability by PCR or sequencing), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2).
Shares MSI and mismatch-repair testing, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, MSI-high (microsatellite instability by PCR or sequencing), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2).