HER2 status in extrahepatic cholangiocarcinoma and gallbladder carcinoma: Concordance between immunohistochemistry and chromogenic in situ hybridization in 140 Cases
In 140 resected bile duct and gallbladder cancers tested the way the zanidatamab trial did, about one in eleven was HER2-positive, and the HER2 signal was often patchy, present in under half the tumour cells.
Overview
Consecutive series of 140 surgically resected biliary tract cancers (87 extrahepatic cholangiocarcinomas, 53 gallbladder carcinomas) collected 2020 to 2025, tested by immunohistochemistry scored on gastric cancer criteria and dual chromogenic in situ hybridisation, with HER2 positivity defined by HERIZON-BTC-01 criteria. Immunohistochemistry was 0 in 72.9 percent, 1+ in 12.1, 2+ in 8.6 and 3+ in 6.4 percent. HER2 positivity was 9.2 percent in extrahepatic cholangiocarcinoma and 9.4 percent in gallbladder carcinoma. ERBB2 amplification was present in all 3+ tumours and some 2+ and rare 1+ cases; the mean ERBB2/CEP17 ratio was 6.2 in 3+ against 3.9 in amplified 2+/1+ tumours (p=0.001). Expression was frequently heterogeneous, often involving under half of tumour cells.
- HER2 positivity 9.4 percent in gallbladder carcinoma and 9.2 percent in extrahepatic cholangiocarcinoma by HERIZON-BTC-01 criteria.
- Immunohistochemistry 3+ in 6.4 percent, 2+ in 8.6 percent; amplification in all 3+ and some 2+ and 1+ cases.
- Intratumoral heterogeneity common, often under 50 percent of cells.
A lower, more conservative prevalence than the 2017 meta-analysis, using the trial's own definition. Heterogeneity means a small biopsy can miss HER2, which argues for testing resection specimens and for reflex testing rather than testing on request.
- Single-centre resected series; advanced unresectable tumours may differ.
- Small gallbladder subgroup (53).
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