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

PLoS One. 2015 Dec 14;10(12):e0144688. doi: 10.1371/journal.pone.0144688. eCollection 2015.

Abstract

Introduction: 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.

Materials and 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / pathology
  • Estrogen Receptor alpha / genetics*
  • Female
  • Gene Expression
  • Humans
  • Image Interpretation, Computer-Assisted / instrumentation*
  • Mammary Glands, Human / pathology*
  • Microscopy / economics*
  • Microscopy / instrumentation
  • Microscopy / methods*
  • Observer Variation
  • Point-of-Care Systems
  • Reproducibility of Results
  • Signal Processing, Computer-Assisted / instrumentation

Substances

  • ESR1 protein, human
  • Estrogen Receptor alpha

Grants and funding

This work was supported by grants from the Swedish Research Council, Sigrid Jusélius Foundation, Finska Läkaresällskapet and Medicinska Understödsföreningen Liv och Hälsa rf. In addition, this study has received funding from the “European Advanced Translational Research Infra Structure in Medicine” (EATRIS)/Academy of Finland and the Innovative Medicines Initiative (IMI)/Predect. The funders had no role in study design, data collection and analysis decision to publish, or preparation of the manuscript.