TissueCypher(™): A systems biology approach to anatomic pathology

Jeffrey W Prichard1, Jon M Davison2, Bruce B Campbell3

  • 1Department of Pathology and Laboratory Medicine, Geisinger Medical Center, Danville, PA 17822, USA.

Insights

This study introduces TissueCypher™, a quantitative imaging method for analyzing epithelial and stromal biomarkers in Barrett's esophagus (BE). This systems biology approach aids in diagnosing high-grade dysplasia (HGD) by identifying significant differences between HGD and reactive atypia (RA) tissues.

Area of Science:

  • Pathology
  • Biomarker Discovery
  • Systems Biology

Background:

  • Histologic diagnosis faces observer variability; immunohistochemistry (IHC) is subjective and focuses on epithelial cells.
  • Tumors involve complex interactions between epithelial and stromal cells, necessitating a systems biology approach.
  • Current diagnostic methods require improved quantification and informatics for actionable clinical scores.

Purpose of the Study:

  • Introduce TissueCypher™, a quantitative, multiplexed biomarker imaging approach using systems biology in anatomic pathology.
  • Describe TissueCypher™ applications for understanding Barrett's esophagus (BE) tissue systems.
  • Evaluate TissueCypher™ as an adjunctive diagnostic tool for BE.

Main Methods:

  • Utilized the TissueCypher™ Image Analysis Platform to assess 14 epithelial and stromal biomarkers in BE biopsies.
  • Analyzed biopsies from patients with nondysplastic BE with reactive atypia (RA) and BE with high-grade dysplasia (HGD).
  • Extracted and evaluated biomarker and morphology features to compare HGD and RA cases.

Main Results:

  • Multiple image analysis features from epithelial and stromal biomarkers, including immune markers and morphology, differed significantly between HGD and RA.
  • Quantitative assessment revealed distinct patterns in biomarker expression and tissue morphology.
  • The approach successfully differentiated between benign reactive changes and high-grade dysplasia in BE.

Conclusions:

  • Assessing epithelial cell abnormalities alongside lamina propria cellular changes can aid BE diagnosis.
  • TissueCypher™ offers a quantitative, systems biology-based adjunct to conventional pathology for BE assessment.
  • This multiplexed imaging approach enhances diagnostic accuracy by integrating diverse tissue biomarkers.
Abstract

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