title: Astronomical algorithms for automated analysis of tissue protein expression in breast cancer.
abstract: BACKGROUND
  High-throughput evaluation of tissue biomarkers in oncology has been greatly accelerated by the widespread use of tissue microarrays (TMAs) and immunohistochemistry. Although TMAs have the potential to facilitate protein expression profiling on a scale to rival experiments of tumour transcriptomes, the bottleneck and imprecision of manually scoring TMAs has impeded progress.
  
  
  METHODS
  We report image analysis algorithms adapted from astronomy for the precise automated analysis of IHC in all subcellular compartments. The power of this technique is demonstrated using over 2000 breast tumours and comparing quantitative automated scores against manual assessment by pathologists.
  
  
  RESULTS
  All continuous automated scores showed good correlation with their corresponding ordinal manual scores. For oestrogen receptor (ER), the correlation was 0.82, P<0.0001, for BCL2 0.72, P<0.0001 and for HER2 0.62, P<0.0001. Automated scores showed excellent concordance with manual scores for the unsupervised assignment of cases to 'positive' or 'negative' categories with agreement rates of up to 96%.
  
  
  CONCLUSIONS
  The adaptation of astronomical algorithms coupled with their application to large annotated study cohorts, constitutes a powerful tool for the realisation of the enormous potential of digital pathology.
authors: Department of Oncology, University of Cambridge, Cambridge CB1 9RN, UK. raza.ali@cancer.org.uk
authors: H R
authors: HR
authors: Ali
authors: M
authors: M
authors: Irwin
authors: L
authors: L
authors: Morris
authors: S-J
authors: SJ
authors: Dawson
authors: F M
authors: FM
authors: Blows
authors: E
authors: E
authors: Provenzano
authors: B
authors: B
authors: Mahler-Araujo
authors: P D
authors: PD
authors: Pharoah
authors: N A
authors: NA
authors: Walton
authors: J D
authors: JD
authors: Brenton
authors: C
authors: C
authors: Caldas
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001331:Automation; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D015331:Cohort Studies; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008875:Middle Aged; D015588:Observer Variation; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015203:Reproducibility of Results; D015996:Survival Rate; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen