Extrahepatic Cholangiocarcinoma (EHCH)

Overview

Extrahepatic cholangiocarcinoma arising from the extrahepatic biliary tree.

hcc_msk_2024 — EHC cases used as a training reference class (together with GBC) for the hidden-genome classifier of intrahepatic cholangiocarcinoma, within a broader MSK biliary/HCC MSK-IMPACT cohort PMID:38864854.

EHC/GBC genetic class characterized by KRAS, SMAD4, and CDKN2A loss; serves as the “biliary-class” reference for IHCH classification PMID:38864854.
Narrative review of etiology-driven genomic landscape of eCCA: KRAS in 37-46%, TP53 in 35-68%, SMAD4 in ~25% (vs. ~4% in iCCA; loss associated with poor prognosis), ARID1A in 14%, CDKN2A/B in 19%, ERBB2 in 3-20%; PSC-associated eCCA shows TP53 (35.5%), KRAS (28.5%), CDKN2A (14.5%), SMAD4 (11.3%), ERBB2 overexpression PMID:25526346.
Review encompasses extrahepatic cholangiocarcinoma (eCCA/dCCA) as part of the CCA spectrum where gut microbiota dysbiosis, bile acid disturbances (NR1H4/FXR downregulation, S1PR2/taurocholic-acid-driven ERK/AKT/NF-kB), and LPS/TLR4 signaling converge to drive tumor progression. PMID:25608663
One of three periampullary tumor cohorts (44 distal bile-duct/cholangiocarcinoma cases); TP53, KRAS, SMAD4, and CDKN2A were the four MutSig-CV-significant genes in this subset; IDH1/IDH2 and BAP1 were essentially absent, distinguishing extrahepatic from intrahepatic cholangiocarcinoma PMID:26804919
In the ICGC 489-CCA cohort, extrahepatic (distal) tumors are enriched in Clusters 1 and 2 (fluke-positive), characterized by ERBB2 amplifications (10.4% fluke-pos), TP53 mutations, and CpG-island hypermethylation; anatomical classification alone was insufficient to predict molecular subtype or prognosis. PMID:28667006

Used as reference to demonstrate that biliary-class IHC has worse OS than non-biliary-class IHC independent of FGFR2/IDH1 alterations PMID:38864854.

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