{"entity":{"id":"paper-bettington-serrated-pathway-colorectal-histopathology-2013","kind":"paper","name":"The serrated pathway to colorectal carcinoma: current concepts and challenges","aka":[],"tldr":"About a third of bowel cancers do not come from the familiar polyp at all. They come from flat, saw-toothed lesions that are hard to see at colonoscopy and follow a different molecular route, driven by chemical silencing of genes rather than by chromosome loss.","summary":"Approximately 30% of colorectal carcinomas develop through a serrated neoplasia pathway, named for the pattern of crypts in the precursor polyps. Molecular abnormalities consistently involve CpG island methylation of low or high degree and activating mutations of BRAF or KRAS; microsatellite instability of high level is often present. That allows a molecular classification into BRAF-mutant CIMP-high tumours, either microsatellite-unstable or stable, and KRAS-mutant CIMP-low microsatellite-stable tumours. Precursor polyps include the sessile serrated adenoma, proximal, with crypt architectural disturbance and BRAF mutation, probably preceded by the microvesicular hyperplastic polyp, with borderline lesions between them. Cytological dysplasia in a sessile serrated adenoma indicates advanced genetic abnormality and a high risk of progression. The traditional serrated adenoma favours the left colon, has tubulovillous architecture, eosinophilic cytoplasm and frequent KRAS mutation. Serrated morphology carcinoma is a World Health Organization subtype with frequent KRAS or BRAF mutation and a poor prognosis.","asOf":"2026-09-24","links":[{"label":"Bettington et al., Histopathology 2013: the serrated pathway to colorectal carcinoma","url":"https://doi.org/10.1111/his.12055"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23339363/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["braf","kras","mmr"],"drugs":[],"companies":[],"institutions":["qimr-berghofer"],"pathways":["epigenetic-reprogramming","mismatch-repair-msi","ras-mapk"],"terms":["msi","sidedness","colonoscopy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Histopathology","year":2013,"doi":"10.1111/his.12055","pmid":"23339363","authors":"Bettington M, Walker N, Clouston A, et al.","paperType":"review","findings":["About 30% of colorectal carcinomas arise through the serrated pathway.","Three molecular classes: BRAF-mutant CIMP-high MSI-high, BRAF-mutant CIMP-high microsatellite stable, KRAS-mutant CIMP-low microsatellite stable.","Cytological dysplasia in a sessile serrated adenoma marks a high risk of progression."],"whatItMeans":"It is the reason colonoscopy quality standards now count sessile serrated lesion detection separately, and the reason a right-sided, BRAF-mutant, MSI-high cancer is read as serrated in origin rather than as an odd adenoma.","caveats":["A review, so the 30% figure is a synthesis rather than a single measurement.","Terminology has since been revised: sessile serrated adenoma is now sessile serrated lesion."],"changedPractice":false},"route":"/key-papers/paper-bettington-serrated-pathway-colorectal-histopathology-2013/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"}],"institution":[{"id":"qimr-berghofer","kind":"institution","name":"QIMR Berghofer Medical Research Institute","route":"/institutions/qimr-berghofer/"}],"pathway":[{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"colonoscopy","kind":"term","name":"Colonoscopy","route":"/terms/colonoscopy/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}]}}