title: Trainable immunohistochemical HER2/neu image analysis: a multisite performance study using 260 breast tissue specimens.
abstract: BACKGROUND
  Aperio Technologies, Inc (Vista, California) provides a new immunohistochemistry (IHC) HER2 Image Analysis (IA) system that allows tuning of the intensity thresholds of the HER2/ neu scoring scheme to adapt to the staining characteristics of different reagents.
  
  
  OBJECTIVE
  To compare the trainable IHC HER2 IA system for different reagents to conventional manual microscopy (MM) in a multisite study.
  
  
  METHODS
  Two hundred sixty formalin-fixed, paraffin-embedded breast cancer specimens from 3 clinical sites were assayed: 180 specimens stained with Dako's HercepTest (Carpinteria, California), and 80 specimens stained with Ventana's PATHWAY HER-2/neu (Tucson, California). At each site, 3 pathologists performed a blinded reading of the glass slides with the use of a light microscope. The glass slides were then scanned and after a wash-out period and randomization, the same pathologists outlined a representative set of tumor regions to be analyzed by IHC HER2 IA. Each of the methods, MM and IA, was evaluated separately and comparatively by using κ statistics of negative HER2/neu scores (0, 1+) versus equivocal HER2/neu scores (2+) versus positive HER2/neu scores (3+) among the different pathologists.
  
  
  RESULTS
  κ Values for IA and MM were obtained across all sites. MM: 0.565-0.864; IA: 0.895-0.947; MM versus IA: 0.683-0.892 for site 1; MM: 0.771-0.837; IA: 0.726-0.917; MM versus IA: 0.687-0.877 for site 2; MM: 0.463-0.674; IA: 0.864-0.918; MM versus IA: 0.497-0.626 for site 3.
  
  
  CONCLUSIONS
  Aperio's trainable IHC HER2 IA system shows substantial equivalence to MM for Dako's HercepTest and Ventana's PATHWAY HER-2/neu at 3 clinical sites. Image analysis improved interpathologist agreement in the different clinical sites.
authors: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. nassar.aziza@mayo.edu
authors: Aziza
authors: A
authors: Nassar
authors: Cynthia
authors: C
authors: Cohen
authors: Sally S
authors: SS
authors: Agersborg
authors: Weidong
authors: W
authors: Zhou
authors: Kathleen A
authors: KA
authors: Lynch
authors: Maher
authors: M
authors: Albitar
authors: Edward A
authors: EA
authors: Barker
authors: Burton L
authors: BL
authors: Vanderbilt
authors: Jim
authors: J
authors: Thompson
authors: Eugene R
authors: ER
authors: Heyman
authors: Holger
authors: H
authors: Lange
authors: Allen
authors: A
authors: Olson
authors: Momin T
authors: MT
authors: Siddiqui
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001940:Breast / Q000737:chemistry* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008853:Microscopy / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human