title: Quantification of Estrogen Receptor-Alpha Expression in Human Breast Carcinomas With a Miniaturized, Low-Cost Digital Microscope: A Comparison with a High-End Whole Slide-Scanner.
abstract: BACKGROUND
  A significant barrier to medical diagnostics in low-resource environments is the lack of medical care and equipment. Here we present a low-cost, cloud-connected digital microscope for applications at the point-of-care. We evaluate the performance of the device in the digital assessment of estrogen receptor-alpha (ER) expression in breast cancer samples. Studies suggest computer-assisted analysis of tumor samples digitized with whole slide-scanners may be comparable to manual scoring, here we study whether similar results can be obtained with the device presented.
  
  
  METHODS
  A total of 170 samples of human breast carcinoma, immunostained for ER expression, were digitized with a high-end slide-scanner and the point-of-care microscope. Corresponding regions from the samples were extracted, and ER status was determined visually and digitally. Samples were classified as ER negative (<1% ER positivity) or positive, and further into weakly (1-10% positivity) and strongly positive. Interobserver agreement (Cohen's kappa) was measured and correlation coefficients (Pearson's product-momentum) were calculated for comparison of the methods.
  
  
  RESULTS
  Correlation and interobserver agreement (r = 0.98, p < 0.001, kappa = 0.84, CI95% = 0.75-0.94) were strong in the results from both devices. Concordance of the point-of-care microscope and the manual scoring was good (r = 0.94, p < 0.001, kappa = 0.71, CI95% = 0.61-0.80), and comparable to the concordance between the slide scanner and manual scoring (r = 0.93, p < 0.001, kappa = 0.69, CI95% = 0.60-0.78). Fourteen (8%) discrepant cases between manual and device-based scoring were present with the slide scanner, and 16 (9%) with the point-of-care microscope, all representing samples of low ER expression.
  
  
  CONCLUSIONS
  Tumor ER status can be accurately quantified with a low-cost imaging device and digital image-analysis, with results comparable to conventional computer-assisted or manual scoring. This technology could potentially be expanded for other histopathological applications at the point-of-care.
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.|Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Oscar
authors.initials: O
authors.lastname: Holmström
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.|Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Linder
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Lundin
authors.affiliation: Center of Microscopy and Nanotechnology, University of Oulu, Oulu, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Moilanen
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Suutala
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
authors.forename: Riku
authors.initials: R
authors.lastname: Turkki
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.|Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.affiliation: BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Isola
authors.affiliation: Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Vinod
authors.initials: V
authors.lastname: Diwan
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.|Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Lundin
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000295:instrumentation*; D042361:Mammary Glands, Human / Q000473:pathology*; D008853:Microscopy / Q000191:economics* / Q000295:instrumentation / Q000379:methods*; D015588:Observer Variation; D019095:Point-of-Care Systems; D015203:Reproducibility of Results; D012815:Signal Processing, Computer-Assisted / Q000295:instrumentation
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha