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Assessing Oral Epithelial Dysplasia Risk for Transformation to Cancer: Comparison Between Histologic Grading Systems

Mark Roger Darling¹, Jason T K Hwang², Benjamin J Dickson³

¹Schulich School of Medicine and Dentistry, The University of Western Ontario.

Applied Immunohistochemistry & Molecular Morphology : AIMM

|May 30, 2023

Summary

The S100A7 immunohistochemical signature system offers a more accurate and reproducible method for predicting oral cancer transformation compared to traditional 2-tier and 3-tier dysplasia grading systems, which showed poor predictive value.

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Establishment and Histological Analysis of Esophageal Organoids Modeling the Progression from Normal to Cancerous Tissues

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Published on: May 30, 2025

Area of Science:

Oral pathology
Biomarker research
Cancer risk assessment

Background:

Traditional 3-tier oral epithelial dysplasia grading is suboptimal for predicting cancer transformation.
A 2-tier system has been proposed but lacks validation.
Objective risk assessment tools are needed for oral dysplasia.

Purpose of the Study:

Compare the predictive accuracy of 3-tier and 2-tier dysplasia grading systems with an S100A7 immunohistochemical signature.
Evaluate inter-observer variability and prediction of oral cancer transformation for each system.

Main Methods:

Retrospective analysis of 48 patient biopsy specimens with known outcomes.
Grading using hematoxylin and eosin stains (2- and 3-tier) and S100A7 immunohistochemistry.
Inter-observer variability assessed with Cohen's kappa; survival analysis using Cox regression.

Main Results:

Both 2- and 3-tier systems showed slight to substantial inter-observer agreement (Kw 0.093-0.624) and poor cancer transformation prediction (P > 0.05).
The S100A7 signature system demonstrated almost perfect inter-observer agreement (Kw = 0.892) and was a significant predictor of transformation (P = 0.047, 0.030).

Conclusions:

Traditional oral dysplasia grading systems have significant limitations in predicting oral cancer risk.
The S100A7 immunohistochemical signature system provides a more objective, quantitative, and reproducible tool for risk assessment.
This novel biomarker signature system shows promise for improving patient management and outcomes in oral potentially malignant disorders.