{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:28:49Z","timestamp":1789658929006,"version":"4.0.1"},"reference-count":145,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the China Scholarship Council","award":["202108420075"],"award-info":[{"award-number":["202108420075"]}],"id":[{"id":"https:\/\/ror.org\/04atp4p48","id-type":"ROR","asserted-by":"crossref"}]},{"award":["202108420075"],"award-info":[{"award-number":["202108420075"]}],"id":[{"id":"https:\/\/ror.org\/04atp4p48","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Research Foundation Flanders","award":["1SHD924N"],"award-info":[{"award-number":["1SHD924N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Villous morphology is routinely used to stratify risk in conventional colorectal adenomas, yet it remains largely interpreted as a visual histological descriptor. This review proposes a different view: villous architecture is a graded, spatially organized epithelial state that links premalignant tissue remodeling to malignant potential. Across histological, molecular, and microenvironmental studies, villous-containing adenomas show convergent features of WNT-driven stem-like expansion, YAP-associated plasticity, fetal-regenerative or fetal-metaplastic transcriptional programs, mucin remodeling, stromal activation, immune attenuation, and genomic instability. These features appear to arise through interacting routes rather than through a single deterministic mutation. This framework helps explain why villous proportion predicts risk imperfectly: it captures a composite biological state but does not resolve its individual components. Quantitative morphometry, spatial transcriptomics, multiplex imaging, and region-resolved genomics could therefore move villous architecture from an observer-dependent category to a continuous, biologically interpretable marker of early malignant transition. Such a shift may improve adenoma classification, refine surveillance strategies, and identify high-risk lesions before conventional thresholds for advanced histology are reached.<\/jats:p>","DOI":"10.3390\/cells15181685","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:59:03Z","timestamp":1789639143000},"page":"1685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Villous Architecture in Colorectal Adenomas: Molecular Pathogenesis, Epithelial Plasticity, and Malignant Risk"],"prefix":"10.3390","volume":"15","author":[{"given":"Zedong","family":"Hu","sequence":"first","affiliation":[{"name":"Digestive Oncology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3398-9249","authenticated-orcid":false,"given":"Tristan","family":"Vanoverbeke","sequence":"additional","affiliation":[{"name":"Digestive Oncology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yin","sequence":"additional","affiliation":[{"name":"Digestive Oncology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Jans","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, UZ Leuven, 3000 Leuven, Belgium"},{"name":"Department of Translational Research in Gastrointestinal Diseases (TARGID), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanmei Carlotta","family":"Arpaia","sequence":"additional","affiliation":[{"name":"Department of Hepato-Gastroenterology, Cliniques Universitaires Saint-Luc, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9994-8226","authenticated-orcid":false,"given":"Raf","family":"Bisschops","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, UZ Leuven, 3000 Leuven, Belgium"},{"name":"Department of Translational Research in Gastrointestinal Diseases (TARGID), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pam\u00e9la","family":"Baldin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cliniques Universitaires Saint-Luc, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3281-8643","authenticated-orcid":false,"given":"Sabine","family":"Tejpar","sequence":"additional","affiliation":[{"name":"Digestive Oncology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium"},{"name":"Department of Gastroenterology and Hepatology, UZ Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1193-0601","authenticated-orcid":false,"given":"Hubert","family":"Piessevaux","sequence":"additional","affiliation":[{"name":"Department of Hepato-Gastroenterology, Cliniques Universitaires Saint-Luc, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","first-page":"170","article-title":"Conventional Colorectal Adenoma","volume":"Volume 1","author":"Hamilton","year":"2019","journal-title":"WHO Classification of Tumours: Digestive System Tumours"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1056\/NEJMra1513581","article-title":"Colorectal Adenomas","volume":"374","author":"Strum","year":"2016","journal-title":"N. 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