# Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer

Source: https://onco.cc/key-papers/paper-hiraoka-her2-status-biliary-hum-pathol-2020/  
OnCo record `paper-hiraoka-her2-status-biliary-hum-pathol-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Testing 454 resected biliary cancers with the stomach cancer HER2 rules, nearly one in three gallbladder cancers was HER2-positive, far more than bile duct cancers inside the liver, but staining was patchy in most positive tumours.

## Summary

HER2 protein expression by immunohistochemistry, HER2 gene amplification by fluorescence in situ hybridisation and both simultaneously by gene-protein assay were examined in 454 surgically resected biliary tract cancers: 110 intrahepatic cholangiocarcinomas, 67 perihilar and 119 distal extrahepatic cholangiocarcinomas, 80 gallbladder carcinomas and 79 ampullary carcinomas. HER2 status was assessed according to the guidelines for HER2 testing in gastro-oesophageal adenocarcinoma.

HER2-positive status was detected in 14.5% of biliary tract cancers: 3.7% of intrahepatic, 3.0% of perihilar and 18.5% of distal cholangiocarcinomas, 31.3% of gallbladder carcinomas and 16.4% of ampullary carcinomas. HER2 positivity tended to correlate with low histological grade. HER2 heterogeneity was common and highly frequent (83%) in positive cases, and reduced HER2 expression in the deeper invasive areas with simultaneous dedifferentiation was frequently observed.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Human Pathology
- Year: 2020
- DOI: 10.1016/j.humpath.2020.08.006
- Authors: Hiraoka N, Nitta H, Ohba A, et al.
- Findings: HER2-positive in 31.3% of 80 gallbladder carcinomas versus 3.7% intrahepatic, 3.0% perihilar, 18.5% distal and 16.4% ampullary.; Heterogeneous HER2 expression in 83% of positive cases, with loss in deeper dedifferentiated areas.; Gastro-oesophageal scoring guideline applied to whole resection specimens.
- What it means: The highest gallbladder HER2 rate in the literature comes from whole resected tumours scored generously; biopsy-based trial screening finds fewer. Heterogeneity is the practical warning for pathologists and for why HER2-directed drugs do not work in every positive tumour.
- Caveats: Resected Japanese patients; advanced disease tested on biopsies may score lower.; Gastric scoring is more permissive than breast scoring.

## Sources

- Hiraoka et al., Hum Pathol 2020: HER2 status in 454 biliary tract cancers: https://doi.org/10.1016/j.humpath.2020.08.006
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32891647/

## Connected records

- cancers: [Ampullary cancer (ampulla of Vater)](https://onco.cc/cancers/ampullary/), [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/)
- targets: [HER2](https://onco.cc/targets/her2/)
- institutions: [National Cancer Center Hospital](https://onco.cc/institutions/ncc-japan/)
- terms: [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [HER2 testing in biliary tract cancer (IHC, ISH and NGS)](https://onco.cc/terms/her2-testing-in-biliary-cancer/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- biomarkers: [HER2 IHC 3+ (HER2-positive by immunohistochemistry)](https://onco.cc/biomarkers/her2-ihc-3-plus/)

---
JSON: https://onco.cc/api/v1/entities/paper-hiraoka-her2-status-biliary-hum-pathol-2020.json