title: Digital image analysis improves the quality of subjective HER-2 expression scoring in breast cancer.
abstract: OBJECTIVE
  To compare HER-2 scoring reproducibility by subjective and digital image analysis (DIA) scores with each other and with fluorescence in situ hybridization (FISH) assessed HER-2 amplification.
  
  
  METHODS
  Herceptest-stained Tissue Micro Arrays of 219 breast carcinomas were scored (DAKO protocol) by 3 observers (both independent and as consensus), scored by DIA and both scores were compared with FISH amplification results.
  
  
  RESULTS
  Interobserver subjective scores reproducibility was good (kappa 0.82 to 0.86) but therapeutically important 3+/2+discrepancies occurred in 11% to 16% of all 3+ cases. Subjective scores and FISH results differed considerably. Consensus scores by 3 pathologists correlated better with FISH, reducing the number of both Immunohistochemical (IHC) negative/FISH positives and IHC 3+/FISH negatives. DIA scores were well reproducible and correlated better with FISH amplification than did subjective scores.
  
  
  CONCLUSIONS
  DIA scores were comparable with consensus scores between 3 expert pathologists, were very well reproducible and performed better in classifying IHC 3+/FISH+ cases than did subjective scores.
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, The Netherlands.
authors.forename: Ivar
authors.initials: I
authors.lastname: Skaland
authors.forename: Irene
authors.initials: I
authors.lastname: Ovestad
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.forename: Jan
authors.initials: J
authors.lastname: Klos
authors.forename: Kjell H
authors.initials: KH
authors.lastname: Kjellevold
authors.forename: Tove
authors.initials: T
authors.lastname: Helliesen
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry*; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D015203:Reproducibility of Results; D046888:Tissue Array Analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human