- Design
- Retrospective single-institution genomic cohort
- Population
- 90 genomically profiled intrahepatic cholangiocarcinomas
- Primary outcome
- Clinicopathological features and survival by FGFR2/3 status
- Effect
- Small-duct 100% vs 32%; DSS HR 0.29 (0.09–0.95) univariate, HR 2.52 (0.14–45.07) adjusted
This retrospective study profiled 90 intrahepatic cholangiocarcinomas with whole-exome and whole-transcriptome sequencing; 25 (28%) carried FGFR2 fusions, FGFR2 mutations or an FGFR3::TACC3 fusion.
FGFR2/3-altered tumours were all small-duct type, arose in younger patients (median 61 vs 68 years), were larger, more often well differentiated and rarely mucin-producing (16% vs 97% of wild-type). They had more BAP1 alterations, fewer TP53 mutations and no ARID1A or KRAS mutations. Disease-specific survival was better on univariate analysis (HR 0.29, 95% CI 0.09–0.95) but not after adjustment (HR 2.52, 0.14–45.07).
The morphological profile — small-duct, non-mucinous, well differentiated — is a useful prompt for ensuring molecular testing is done, since FGFR inhibitors are a treatment option for these patients. The prognostic advantage appears to come from the accompanying features rather than FGFR status itself.
- Ensure FGFR2 fusion testing for intrahepatic cholangiocarcinoma, especially small-duct, non-mucinous tumours.
- Use an RNA-based or fusion-capable assay; FGFR2 partners are numerous and varied.
- Report histological subtype (small-duct vs large-duct) explicitly — it predicts the molecular profile.
- Do not use FGFR status alone as a favourable prognostic marker.
Why it matters
Morphology can flag which cholangiocarcinomas are most likely to carry a targetable FGFR2 alteration.
Don't overread it
Single-centre, 90 cases; the survival difference did not survive multivariate analysis.
The statistics, in plain English
The survival advantage (HR 0.29) disappeared after adjustment for other factors, and the adjusted interval (0.14–45) is so wide it is uninformative. With 25 altered cases, the study cannot settle prognosis.
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