title: A new immunohistochemical ER/PR image analysis system: a multisite performance study.
abstract: BACKGROUND
  Aperio provides a new image analysis (IA) solution for immunohistochemistry (IHC) as part of its digital pathology system. To be used in a clinical setting, substantial equivalence to scoring by manual microscopy (MM) needs to be shown. A multisite study was conducted to assess the performance of Aperio's IHC IA solution for estrogen receptor (ER) and progesterone receptor (PR).
  
  
  METHODS
  A total of 260 formalin-fixed, paraffin-embedded breast tissue specimens were assayed at 2 clinical sites for ER and PR. The ability to score ER/PR slides in terms of (1) percentage of positive nuclei with cutoffs of 1%, 5%, and 10% and (2) average staining intensity as 0, 1+, 2+, and 3+ score was assessed. At each site, 3 pathologists performed a blinded read of the glass slides using their microscopes. The glass slides were then scanned, and after a wash-out period and randomization of the slides, the pathologists viewed the images on a computer monitor and outlined a representative set of tumor regions to be analyzed by IA. Each of the methods: MM and IA were evaluated separately and comparatively.
  
  
  RESULTS
  Comparable or higher percent agreements were obtained for IA compared with MM (ER--percent of positive nuclei with cutoffs: MM: 91.3% to 98.8%/IA: 93.8% to 98.8%/IA vs. MM: 92.5% to 97.5%, and intensity score: MM: 55.0% to 86.3%/IA: 88.8% to 90.0%/IA vs. MM: 63.8% to 86.3%; PR-percent of positive nuclei with cutoffs: MM: 83.8% to 99.0%/IA: 85.0% to 99.0%/IA vs. MM: 81.3% to 99.0%, and intensity score: MM: 58.8% to 88.0%/IA: 68.8% to 88.0%/IA vs. MM: 58.8% to 84.0%).
  
  
  CONCLUSIONS
  The study results show that Aperio's digital IHC IA solution for ER/PR is substantially equivalent to scoring by MM.
authors.affiliation: Department of Pathology, Mayo Clinic, Rochester, MN, USA. nassar.aziza@mayo.edu
authors.forename: Aziza
authors.initials: A
authors.lastname: Nassar
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
authors.forename: Sally S
authors.initials: SS
authors.lastname: Agersborg
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhou
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Lynch
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Heyman
authors.forename: Allen
authors.initials: A
authors.lastname: Olson
authors.forename: Holger
authors.initials: H
authors.lastname: Lange
authors.forename: Momin T
authors.initials: MT
authors.lastname: Siddiqui
mesh_terms: D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D008853:Microscopy; D015588:Observer Variation; D017410:Practice Guidelines as Topic; D011960:Receptors, Estrogen / Q000276:immunology / Q000378:metabolism; D011980:Receptors, Progesterone / Q000276:immunology / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone