Authors
Marc Andreu-Inglés, Alina-Iuliana Onoiu, Marc Grifoll-Escoda, Anna Hernández-Aguilera, Josep Gumà-Padró, Francesc Riu, Karla Peña, Jordi Camps, David Parada
Published in
International journal of molecular sciences. Volume 27. Issue 19. Oct 08, 2026. Epub Oct 08, 2026.
Abstract
Bladder cancer surveillance remains challenging because conventional methods do not fully capture the biological heterogeneity within histologically low-grade urothelial carcinoma (LGUC). We evaluated whether urinary DNA methylation profiling using Bladder EpiCheck™ can identify clinically relevant LGUC subgroups in a retrospective single-center cohort of 134 patients with paired histopathology, urine cytology, and methylation results. Methylation positivity increased across negative histopathology, LGUC, and high-grade urothelial carcinoma (HGUC) (18.4%, 51.4%, and 91.5%, respectively). Within LGUC, 19 of 37 tumors (51.4%) were methylation-positive. Their EpiScores overlapped those of HGUC, whereas methylation-negative LGUCs exhibited scores similar to negative histopathology. Gaussian mixture modeling independently supported a bimodal distribution. Methylation-positive LGUCs demonstrated a higher Ki67 labeling index, more frequent MTAP loss (33.3% vs. 11.8%), and more recurrences, including recurrence as HGUC, than methylation-negative LGUCs. Conventional nuclear morphometry did not distinguish between the two LGUC subgroups. These exploratory findings suggest that urinary DNA methylation may identify a biologically distinct subset of histologically low-grade tumors with selected high-grade-associated features. Prospective external validation is required before methylation status can inform surveillance or treatment decisions.
PMID:
42884175
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.
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