Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer
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.
Overview
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.
- 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.
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.
- Resected Japanese patients; advanced disease tested on biopsies may score lower.
- Gastric scoring is more permissive than breast scoring.
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