Abstract
Ulcerative colitis (UC) is associated with an elevated risk of colorectal cancer (CRC), driven by chronic inflammation and a distinct inflammation-dysplasia-carcinoma pathway. Conventional surveillance relies on colonoscopy and histologic assessment, but flat, multifocal dysplasia and sampling limitations challenge early detection. Tissue-based biomarkers offer promise in improving risk stratification and identifying patients at high risk for UC-associated CRC (UC-CRC). This review explores key categories of tissue biomarkers with potential clinical utility, including genetic mutations, epigenetic alterations, microRNA expression profiles, and markers of genomic instability such as telomere shortening, copy number variants, and aneuploidy. Many of these molecular alterations precede histologic dysplasia and reflect a "field effect," suggesting their potential role in early cancer detection. Despite compelling associations between these biomarkers and neoplastic progression, most lack prospective validation and are not yet ready for routine clinical use. Future research should prioritize the development of integrated biomarker panels and validate their predictive accuracy in longitudinal UC cohorts. Molecular profiling may ultimately enable personalized, risk-adapted surveillance strategies that improve early detection while minimizing unnecessary interventions.