title: Her2/neu testing in gastric cancer: evaluating the risk of sampling errors.
abstract: BACKGROUND
  We evaluated the risk of sampling errors in specimens of biopsy size, which may be caused by heterogeneous overexpression of Her2/neu in gastric cancer (GC).
  
  
  METHODS
  The study cohort comprised 454 gastrectomy patients with adenocarcinoma of the stomach or esophago-gastric junction. Tissue micro-arrays (TMAs) served as 'biopsy procedure' and were generated from formalin-fixed and paraffin-embedded tissue: five tissue cylinders were collected randomly from each tumor, rendering 2230 core cylinders. These were compared with 454 whole tissue sections obtained from the same paraffin blocks. Her2/neu expression and gene amplification were analyzed by immunohistochemistry and in situ hybridization. The Her2/neu status was determined according to GC scoring system by two independent observers.
  
  
  RESULTS
  In whole tissue sections, 37 (8.1%; observer 1) and 38 (8.4%; observer 2) of the GCs, and in the corresponding TMAs, 28 (6.3%; observer 1) and 28 (6.3%; observer 2) of the GCs were classified as Her2/neu-positive (kappa value 98.5% and 96.2%; P < 0001). Comparison of whole tissue sections with corresponding TMAs showed a false-negative rate of 24% and a false-positive rate of 3% for TMAs.
  
  
  CONCLUSIONS
  Assessment of the Her2/neu status in tissue biopsies carries a significant risk of sampling errors, thereby rendering patients unsuitable for treatment with trastuzumab.
authors.affiliation: Department of Pathology, Christian-Albrechts University, D-24105 Kiel, Germany.
authors.forename: V S
authors.initials: VS
authors.lastname: Warneke
authors.forename: H-M
authors.initials: HM
authors.lastname: Behrens
authors.forename: C
authors.initials: C
authors.lastname: Böger
authors.forename: T
authors.initials: T
authors.lastname: Becker
authors.forename: F
authors.initials: F
authors.lastname: Lordick
authors.forename: M P A
authors.initials: MP
authors.lastname: Ebert
authors.forename: C
authors.initials: C
authors.lastname: Röcken
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D012306:Risk; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human