- Design
- Retrospective single-institution series with whole-exome and transcriptome sequencing
- Population
- 90 intrahepatic cholangiocarcinomas (25 FGFR2/3-altered)
- Primary outcome
- Clinicopathological and molecular features; survival
- Effect
- All FGFR-altered tumours small-duct; DSS HR 0.29 (95% CI 0.09 to 0.95) unadjusted, not significant after adjustment
A five-year retrospective series profiled 90 intrahepatic cholangiocarcinomas by whole-exome and whole-transcriptome sequencing; 25 (28%) carried FGFR2 fusions, an FGFR3–TACC3 fusion, or FGFR2 mutations.
FGFR-altered tumours came from younger patients and were larger, more often well differentiated, almost all non-mucin-producing, and all of the small-duct type. They had more BAP1 alterations and fewer TP53, ARID1A and KRAS mutations. Disease-specific survival was better on univariable analysis (HR 0.29, 95% CI 0.09 to 0.95), but not after adjustment.
The morphology gives pathologists a clue to which tumours are most likely to carry a targetable fusion. The survival finding is fragile, and the authors attribute it to the tumours' overall biology rather than the FGFR change itself.
In practice, small-duct, non-mucinous intrahepatic cholangiocarcinoma is the group in which molecular testing for FGFR2 fusions is most likely to find a target.
- Report the small-duct versus large-duct subtype in every intrahepatic cholangiocarcinoma
- Prioritise FGFR2 fusion testing in small-duct, non-mucinous tumours
- Use an RNA-based or fusion-capable assay, as FGFR2 has many fusion partners
- KRAS and TP53 mutations were linked to worse overall survival in this series
Why it matters
Morphology can guide which cholangiocarcinomas most need molecular testing.
Don't overread it
The survival advantage disappeared after adjustment and should not be quoted as prognostic.
The statistics, in plain English
The unadjusted hazard ratio of 0.29 suggested better survival, but after adjusting for other factors the estimate became 2.52 with a confidence interval from 0.14 to 45, meaning the data cannot say anything reliable about FGFR status and survival on its own.
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