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Published on: November 26, 2015
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.
Background:
Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC) methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making.
Aims:
Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE) and the potential use as an adjunctive tool in the diagnosis of BE are described.
Patients And Methods:
The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22) and Barrett's with high-grade dysplasia (HGD, n = 17). Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA.
Results:
Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA.
Conclusions:
The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional pathology in the assessment of BE.
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