Liquid Biopsy Biomarkers for Endoscopic Surveillance in Lynch Syndrome

Lynch syndrome (LS) is an autosomal dominant hereditary condition that markedly increases the risk of colorectal cancer (CRC) and other malignancies. Standard surveillance relies on colonoscopy every 1-2 years starting at age 20-25 years, an invasive and costly procedure that may become burdensome during lifelong follow-up and may miss interval cancers. This prospective, single-institution, observational study aims to identify minimally invasive plasma, stool, and urine biomarkers that could improve the detection of early colorectal lesions in individuals with LS and help refine surveillance protocols. Biomarker analyses include microsatellite instability (MSI) and MMR-related frameshift mutations in circulating tumor DNA, plasma and stool microRNA profiling, stool microbiome analysis, and exploratory urine cell-free DNA banking. Patients with genetically confirmed LS followed at Fondazione IRCCS Istituto Nazionale dei Tumori will be enrolled and followed for 24 months, undergoing surveillance colonoscopy at baseline, 12 months, and 24 months, with periodic venous blood sampling and stool, urine, and tissue collection according to protocol.