Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma
Among 308 Western bile duct cancers only about one in 75 was microsatellite unstable, but those few had unusual microscopy, more immune cells and better survival, so testing is still worthwhile because immunotherapy works for them.
Overview
A cohort of 308 Western-world, non-liver-fluke-associated cholangiocarcinomas (159 intrahepatic, 106 perihilar and 43 distal) was analysed with the mononucleotide microsatellite instability marker panel BAT25, BAT26 and CAT25; MSI-high was detected in 4 of 308 (1.3%).
Patients with MSI-high tumours mostly had an atypical histomorphology (P = 0.004), showed longer overall survival despite high tumour stage, and were younger. MSI-high tumours carried higher numbers of CD8-positive T cells, FOXP3-positive regulatory T cells and CD20-positive B cells and high or at least moderate MHC class I expression.
- MSI-high in 4 of 308 cholangiocarcinomas (1.3%).
- MSI-high tumours: atypical histomorphology (P = 0.004), younger patients, longer survival despite higher stage.
- Higher CD8, FOXP3 and CD20 infiltrates and higher MHC class I in MSI-high tumours.
A Western benchmark for how rare MSI-high is in bile duct cancer; gallbladder cancer was not included, and the MSK gallbladder cohort's 2.5% by MSIsensor and the Indian 0.6% by panel bracket it.
- Cholangiocarcinoma only, no gallbladder tumours.
- Three-marker PCR panel; sequencing-based MSI calls may differ.
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