title: Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections.
abstract: OBJECTIVE
  To assess human epidermal growth factor receptor 2 (HER2) status and heterogeneity using immunohistochemistry (IHC) and silver in-situ hybridization (SISH) in gastric carcinoma and dysplasia, and to correlate HER2 status between biopsy and resection specimens of gastric carcinoma.
  
  
  RESULTS
  Immunohistochemistry for HER2 was performed in 178 cases of gastric carcinoma, and SISH in cases showing at least 1+ reaction. HER2 positivity [European Medicines Agency (EMA) guidelines] was identified in 20.2% of carcinomas and 12.9% of high-grade dysplasia, and HER2 heterogeneity noted in 50% and 33% of these cases, respectively. IHC negative/positive reactivity and SISH results were concordant in 96.2%. SISH amplification was seen in 35.3% of IHC 2+ and in a case with previously unrecognized staining pattern. Concordance of IHC HER2 status on biopsies and gastrectomies was seen in 74.1%. False negative IHC results on either the biopsy or gastrectomy were seen in 19.4% of HER2 amplified cases.
  
  
  CONCLUSIONS
  Human epidermal growth factor receptor 2 status in gastric carcinoma is comparable to previous studies with good concordance between IHC and SISH; all IHC 2+ and unusual patterns should be assessed with ISH studies; heterogeneity of tumour HER2 overexpression/amplification is common with possible implications for HER2 testing; and HER2 overexpression appears sufficiently specific to be considered a potential diagnostic biomarker of dysplasia.
authors.affiliation: PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, University of Western Australia, Perth, WA, Australia. stephenlee.au@gmail.com
authors.forename: Stephen
authors.initials: S
authors.lastname: Lee
authors.forename: Willem Bastiaan
authors.initials: WB
authors.lastname: de Boer
authors.forename: Soraya
authors.initials: S
authors.lastname: Fermoyle
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.forename: Marian Priyanthi
authors.initials: MP
authors.lastname: Kumarasinghe
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D001706:Biopsy; D005743:Gastrectomy; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D011230:Precancerous Conditions / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human