EPCAM germline deletion (3' end) silences downstream MSH2 by promoter hypermethylation →...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-EPCAM-GERMLINE-CRC |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-CRC |
| Sources | SRC-ESMO-COLON-2024 SRC-NCCN-COLON-2025 |
Actionability Facts
| Biomarker | BIO-DMMR-IHC |
|---|---|
| Variant | EPCAM germline 3' deletion (silences MSH2 by promoter methylation) → Lynch |
| Disease | DIS-CRC |
| ESCAT tier | IA |
| Recommended combinations | pembrolizumab monotherapy (1L mCRC dMMR, KEYNOTE-177), nivolumab + ipilimumab (2L+, CheckMate-142) |
| Contraindicated monotherapy | FOLFOX/FOLFIRI 1L in dMMR mCRC (inferior to ICI), adjuvant 5-FU monotherapy in stage II dMMR |
| Evidence summary | EPCAM germline deletion (3' end) silences downstream MSH2 by promoter hypermethylation → Lynch syndrome with isolated MSH2/MSH6 protein loss on IHC. Treat as MSH2-equivalent Lynch: pembrolizumab 1L mCRC dMMR (KEYNOTE-177); pan- tumor MSI-H ICI eligibility supersedes tumor-specific lines. ESCAT IA / OncoKB Level 1. |
Notes
EPCAM-Lynch is rarer than MLH1/MSH2/MSH6/PMS2 Lynch (~1-3% of Lynch cases). Cascade testing mandatory; family-line implications identical to MSH2 Lynch. Pan-tumor MSI-H ICI eligibility supersedes tumor-specific lines.
Used By
No reverse references found in the YAML corpus.