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The serrated pathway is the second route to bowel cancer, running not through the familiar mushroom-shaped polyp but through flat, pale, saw-toothed lesions that are easy to miss at colonoscopy and rarely bleed. It accounts for about three in ten bowel cancers and for most of the ones whose DNA proofreading has broken down by accident rather than by inheritance.
About 30 percent of colorectal carcinomas develop through a serrated route, named for the saw-tooth pattern of the crypts in the precursor polyps. The molecular signature is methylation of CpG islands, of low or high degree, with an activating mutation in BRAF or KRAS; microsatellite instability is often present, which allows serrated pathway cancers to be grouped as BRAF-mutant and highly methylated with either unstable or stable microsatellites, or KRAS-mutant with low methylation and stable microsatellites (Bettington 2013). The precursors are the microvesicular hyperplastic polyp, the sessile serrated lesion (proximal, with distorted crypt architecture and BRAF mutation) and the traditional serrated adenoma (left-sided, tubulovillous, eosinophilic, more often KRAS-mutant). Cytological dysplasia in a sessile serrated lesion marks a sharply higher risk of progression. Serrated adenocarcinoma, a separate World Health Organization subtype with well-differentiated, mucinous or trabecular patterns, is the carcinoma this route produces and has its own record.
Why it matters for screening and surveillance. Serrated lesions are flat, pale and often covered by a mucus cap, so they are harder to see and harder to remove completely than adenomas; they bleed rarely, so faecal tests detect few of them; and missed serrated polyps are a recognised contributor to preventable colorectal cancers. A detection-rate benchmark for sessile serrated polyps and serrated-specific surveillance strategies are the current responses (Expert Rev Gastroenterol Hepatol 2025). Histological separation of a hyperplastic polyp from a sessile serrated lesion remains difficult and is a source of variation between pathologists, which feeds straight through into the surveillance interval a patient is given. The UK surveillance guidelines count a serrated polyp of at least 10 mm, or one containing any grade of dysplasia, as an advanced colorectal polyp (Rutter 2020).
In plain words · BRAF is a signalling kinase mutated in half of melanomas; blocking it with two drugs at once became a template for targeted therapy.
Showing the target this term concerns: BRAF.
Shares Interval cancer, Surveillance intervals after polypectomy, Colonoscopy, Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood) and the tags gi, colorectal.
Shares Consensus molecular subtypes (CMS1-4), Histopathology & immunohistochemistry, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Mismatch-repair deficient (MSI-high) colorectal cancer and the tags gi, colorectal.
Shares Interval cancer, Colonoscopy, Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), Colon cancer (adenocarcinoma of the colon) and the tags gi, colorectal.
Shares MLH1 promoter methylation (sporadic versus Lynch mismatch repair loss), Colonoscopy, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer and the tags gi, colorectal.
Shares Adenoma-carcinoma sequence, Consensus molecular subtypes (CMS1-4), Colon cancer (adenocarcinoma of the colon), Colorectal cancer and the tags gi, colorectal.
Shares Interval cancer, Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), Colon cancer (adenocarcinoma of the colon), Colorectal cancer and the tags gi, colorectal.
Shares Polyp types in the bowel, Surveillance intervals after polypectomy, Adenoma-carcinoma sequence, Lynch syndrome-associated colorectal cancer and the tags gi, colorectal.
Shares BRAF V600E-mutant colorectal cancer, BRAF, KRAS, Colon cancer (adenocarcinoma of the colon) and the tags gi, colorectal.