title: The validation of a novel method combining both HER2 immunohistochemistry and HER2 dual-colour silver in situ hybridization on one slide for gastric carcinoma testing.
abstract: BACKGROUND
  HER2 status assessment is a prerequisite for the establishment of an appropriate treatment strategy in gastric cancer. Gastric cancers are very heterogeneous and separate evaluations of gene amplification and protein expression lead to uncertainties in localizing distinct clones and are time consuming. This study evaluates the equivalence of the novel method combining both gene and protein platforms on one slide.
  
  
  METHODS
  Immunohistochemistry (IHC) and HER2 dual-colour silver in situ hybridization (SISH) as single methods (IHC/SISH) and gene-protein platform combining both methods on one slide (gene/protein) were performed in randomly collected 100 cases of gastric adenocarcinoma. Results of IHC/SISH were compared with gene/protein staining.
  
  
  RESULTS
  96 of 100 samples were assessable. In the gene/protein staining, pathologists were able to assess gene amplification and consequent protein expression at the single cell level. In comparison trials, gene amplification was observed in 14.6% by both, conventional SISH and gene/protein platform (agreement 100%; Kappa-coefficient κ = 1.0). Protein expression scores by IHC were 70.8% (0), 10.4% (1+), 9.4% (2+), and 9.4% (3+). Protein expression by gene/protein method were: 70.8% (0), 11.5% (1+), 7.3% (2+) and 10.4% (3+) of patients. There were complete concordances in IHC assessment of cases with score 0 (100.0%; κ = 1). High concordances are shown in score 1+ (98.96%; κ = 0.947) and 3+ (96.88%; κ = 0.825) cases and good concordances in 2+ cases (95.83%; κ = 0.728).
  
  
  CONCLUSIONS
  This novel combined platform has the advantage of being able to evaluate both gene and the protein status in the same cancer cell and may be of particular interest for research and patient's care.
  Disease Biomarker.
authors.affiliation: Institute of Clinical Cancer Research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center Frankfurt, Steinbacher Hohl 2-26, 60488, Frankfurt/Main, Germany. werner.dominique@khnw.de.
authors.forename: Dominique
authors.initials: D
authors.lastname: Werner
authors.forename: Achim
authors.initials: A
authors.lastname: Battmann
authors.forename: Kristina
authors.initials: K
authors.lastname: Steinmetz
authors.forename: Tobin
authors.initials: T
authors.lastname: Jones
authors.forename: Tiffany
authors.initials: T
authors.lastname: Lamb
authors.forename: Michele
authors.initials: M
authors.lastname: Martinez
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Altmannsberger
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012834:Silver / Q000737:chemistry; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D012834:Silver; C508053:ERBB2 protein, human