Epigenetic biomarkers in diagnostic pathology: from analytical validity to diagnostic evidence

Abstract

Epigenetic alterations are increasingly being evaluated as diagnostic biomarkers and risk-stratification tools in surgical pathology and cytopathology. The clinical implementation of epigenetic biomarkers requires more than the demonstration of disease-associated molecular changes. DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs may provide clinically relevant information, but their clinical value depends on reproducibility, specimen adequacy, analytical robustness, interpretability, and suitability for clinical reporting. These requirements are particularly relevant in cytopathology and molecular testing of body fluid specimens, where specimens may have low cellularity or suboptimal nucleic acid quality, and morphological interpretation may be equivocal. Urothelial carcinoma represents an informative model because urine-based methylation assays illustrate both the potential and the limitations of epigenetic translation. These assays have been explored as adjunctive tools to cytology in selected diagnostic and surveillance settings, without replacing guideline-based cystoscopic follow-up. This editorial introduces the Special Issue “Epigenetics in Diagnostic Pathology: Translational Biomarkers, Technologies, and Clinical Impact” and supports a translational approach grounded in diagnostic pathology, in which epigenetic biomarkers are evaluated according to their capacity to generate reliable diagnostic evidence in routine clinical specimens.

Keywords

epigenetics / diagnostic pathology / DNA methylation / biomarkers / liquid biopsy / molecular pathology / translational medicine

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