MSH2 germline loss-of-function in urothelial produces dMMR/MSI-H phenotype. Pan-tumor MSI...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-MSH2-GERMLINE-UROTHELIAL |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-UROTHELIAL |
| Sources | SRC-CIVIC SRC-EAU-PROSTATE-2024 SRC-NCCN-BLADDER-2025 |
Actionability Facts
| Biomarker | BIO-DMMR-IHC |
|---|---|
| Variant | MSH2 germline loss-of-function (dMMR / MSI-H) |
| Disease | DIS-UROTHELIAL |
| ESCAT tier | IA |
| Recommended combinations | pembrolizumab monotherapy (pan-tumor MSI-H, FDA 2017), standard urothelial therapy (cisplatin or ICI 1L per PD-L1) |
| Evidence summary | MSH2 germline loss-of-function in urothelial produces dMMR/MSI-H phenotype. Pan-tumor MSI-H ICI eligibility (pembrolizumab per KEYNOTE-158, dostarlimab per GARNET) supersedes tumor-specific lines via tissue-agnostic FDA approval. MSI-H in urothelial is rare (~3-5%); pembrolizumab tissue-agnostic applies. |
Notes
Germline MSH2 loss → cascade testing mandatory (Lynch syndrome). Family meets Amsterdam/Bethesda criteria. Pan-tumor MSI-H ICI eligibility supersedes tumor- specific lines.
Used By
No reverse references found in the YAML corpus.