#AI reads Urine# Detection of urothelial carcinoma in Lynch syndrome using microsatellite instability analysis of urine cell-free DNA
Published 04 November, 2025
This study focuses on detecting Lynch syndrome-related urothelial carcinoma using microsatellite instability (MSI) analysis of urine cell-free DNA. It was conducted through two cohorts:
1. For 50 patients with upper tract urothelial carcinoma (UTUC), 3 cases (6.00%) were identified as MSI-H (high microsatellite instability) and mismatch repair-deficient (MMRd). The urine MSI analysis achieved 100% sensitivity and 100% specificity for symptomatic UTUC, and 3 new Lynch syndrome cases were confirmed .
2. Among 142 eligible individuals with MSH2-Lynch syndrome (aged 30-75 years, no recent cancer diagnosis), 81 (57.0%) participated. After excluding 1 individual diagnosed with urothelial carcinoma post-enrollment, 5 out of the remaining 80 cases (6.25%) showed MSI-H in urine, and 4 of these 5 were subsequently diagnosed with urothelial carcinoma. None of the 75 individuals with microsatellite-stable (MSS) urine were diagnosed with urothelial carcinoma during follow-up. This analysis demonstrated 100% sensitivity, 98.7% specificity, 80% positive predictive value, and 100% negative predictive value for asymptomatic Lynch syndrome-related urothelial carcinoma .
The study indicates that this low-cost urine MSI test, suitable for routine surveillance, enables the early diagnosis of asymptomatic Lynch syndrome-related urothelial carcinoma. However, further studies are needed to confirm its accuracy and patient outcomes. Compared with traditional methods such as urinalysis and urine cytology, this test has higher sensitivity and specificity. Meanwhile, it has limitations including a small sample size and focus only on MSH2-Lynch syndrome, and future plans involve expanding the sample size and including patients with other Lynch syndrome genotypes for further research.
EBioMedicine. 2025 Oct 24:121:105969. doi: 10.1016/j.ebiom.2025.105969.
Youhe Gao
Statement: During the preparation of this work the author(s) used Doubao / AI reading for summarizing the content. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the published article.
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