title: Pathologic diagnostics of HER2 positivity in gastroesophageal adenocarcinoma.
abstract: OBJECTIVE
  The human epidermal growth factor receptor 2 (HER2) oncogene shows overexpression in 15% to 30% of gastroesophageal adenocarcinomas. Targeted anti-HER2 therapy with trastuzumab has been recently validated in advanced gastric and gastroesophageal junction cancer treatment. A standardized modified scoring system was recently introduced for gastroesophageal HER2 scoring. We aimed to validate this scoring system, including an analysis of interobserver variability of immunohistochemistry (IHC) scoring.
  
  
  METHODS
  In total, 323 patients with histologically confirmed invasive gastric or esophageal adenocarcinoma were examined for HER2 by IHC and chromogenic in situ hybridization (CISH). IHC 3 + or IHC 2 +/CISH positive tumors were considered HER2 positive. Interobserver variability on IHC scoring using the currently standard modified HER2 scoring system was determined among three clinical pathologists. Clinicopathologic characteristics were retrospectively retrieved from the patient records.
  
  
  RESULTS
  HER2 positivity was found in 50 (15.5%) of 323 patients. Interobserver agreement on IHC scoring was high (κ = 0.78). Most disagreement was found in diffuse or mixed tumor types and in weak to moderate stained samples (IHC 2 +). The HER2 IHC scoring system is sensitive in differentiating HER2 status before ISH.
  
  
  CONCLUSIONS
  The currently used standardized HER2 scoring system is an excellent, clinically applicable method to establish HER2 status in appropriately educated and trained pathologists.
authors.affiliation: From the Departments of Medical Oncology and.
authors.forename: Timco
authors.initials: T
authors.lastname: Koopman
authors.affiliation: Pathology, Deventer Hospital, Deventer, the Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Louwen
authors.affiliation: Pathology, Deventer Hospital, Deventer, the Netherlands.
authors.forename: Mariska
authors.initials: M
authors.lastname: Hage
authors.affiliation: Pathology, Deventer Hospital, Deventer, the Netherlands.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: From the Departments of Medical Oncology and A.Imholz@dz.nl.
authors.forename: Alex L T
authors.initials: AL
authors.lastname: Imholz
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: Esophageal cancer; Gastric cancer; Gastroesophageal cancer; Human epidermal growth factor 2 (HER2); Immunohistochemistry (IHC)