title: Continuous measurement of breast tumour hormone receptor expression: a comparison of two computational pathology platforms.
abstract: OBJECTIVE
  Computational pathology platforms incorporate digital microscopy with sophisticated image analysis to permit rapid, continuous measurement of protein expression. We compared two computational pathology platforms on their measurement of breast tumour oestrogen receptor (ER) and progesterone receptor (PR) expression.
  
  
  METHODS
  Breast tumour microarrays from the Nurses' Health Study were stained for ER (n=592) and PR (n=187). One expert pathologist scored cases as positive if ≥1% of tumour nuclei exhibited stain. ER and PR were then measured with the Definiens Tissue Studio (automated) and Aperio Digital Pathology (user-supervised) platforms. Platform-specific measurements were compared using boxplots, scatter plots and correlation statistics. Classification of ER and PR positivity by platform-specific measurements was evaluated with areas under receiver operating characteristic curves (AUC) from univariable logistic regression models, using expert pathologist classification as the standard.
  
  
  RESULTS
  Both platforms showed considerable overlap in continuous measurements of ER and PR between positive and negative groups classified by expert pathologist. Platform-specific measurements were strongly and positively correlated with one another (r≥0.77). The user-supervised Aperio workflow performed slightly better than the automated Definiens workflow at classifying ER positivity (AUCAperio=0.97; AUCDefiniens=0.90; difference=0.07, 95% CI 0.05 to 0.09) and PR positivity (AUCAperio=0.94; AUCDefiniens=0.87; difference=0.07, 95% CI 0.03 to 0.12).
  
  
  CONCLUSIONS
  Paired hormone receptor expression measurements from two different computational pathology platforms agreed well with one another. The user-supervised workflow yielded better classification accuracy than the automated workflow. Appropriately validated computational pathology algorithms enrich molecular epidemiology studies with continuous protein expression data and may accelerate tumour biomarker discovery.
authors.affiliation: Departments of Surgery and Biochemistry, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Thomas P
authors.identifier: http://orcid.org/0000-0003-0440-8727
authors.initials: TP
authors.lastname: Ahern
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, Massachusetts, USA.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Rosner
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Glass
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Frieling
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Collins
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, Massachusetts, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Rulla M
authors.initials: RM
authors.lastname: Tamimi
mesh_terms: D000328:Adult; D000465:Algorithms; D057205:Automation, Laboratory; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007150:Immunohistochemistry; D008875:Middle Aged; D012372:ROC Curve; D011960:Receptors, Estrogen / Q000032:analysis* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000032:analysis* / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: BREAST CANCER; COMPUTER ASSISTED; MOLECULAR PATHOLOGY; STEROID RECEPTORS