Metaplasia, dysplasia, carcinoma in situ: the flat route to gallbladder cancer
Most gallbladder cancers grow out of flat, invisible changes in the lining: years of irritation from stones turn the mucosa metaplastic, then dysplastic, then into carcinoma in situ, and finally into invasive cancer, a process estimated at 10 to 15 years.
Overview
The flat pathway is the dominant carcinogenic route in the gallbladder. Metaplasia, dysplasia and carcinoma in situ were present in the mucosa adjacent to 66%, 81.3% and 69% of invasive cancers, and dysplasia unassociated with cancer was seen in about 1% of cholecystectomies for symptomatic stones; the mean ages of patients with isolated dysplasia (51.9 years), early carcinoma (56.8) and advanced carcinoma (62.9) form a gradient that puts the sequence at roughly 10 years (Roa 2006), or around 15 years in the earlier series of 84 dysplasias, 60 early and 181 advanced carcinomas (Roa 1996). In the WHO scheme these flat lesions are graded as biliary intraepithelial neoplasia (BilIN), low or high grade. Exome sequencing of co-existing low-grade BilIN, high-grade BilIN and carcinoma from the same gallbladders showed ageing as the main source of mutations, CTNNB1 as a critical early event and two evolutionary paths: the stepwise sequence, and a carcinoma that diverged early after extensive loss of heterozygosity and evolved independently of the visible precursor (Lin 2021). The raised alternative, adenoma or intracholecystic papillary-tubular neoplasm, has its own page.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · CTNNB1 (Catenin beta-1) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and an approved or late-stage drug is recorded against it. Tied to Hepatocellular carcinoma, Colorectal cancer, Ovarian cancer and 5 more.
Showing the target this term concerns: CTNNB1.
Molecular confirmation that the visible precursor is not always the parent of the cancer beside it, which tempers hopes that finding and removing dysplasia catches every tumour, and puts Wnt signalling through CTNNB1 at the start of the raised route.
The morphological argument that gallbladder cancer is a flat-dysplasia disease, which is why it is invisible on imaging until late and why prevention rests on removing the diseased gallbladder rather than on polyp surveillance alone.
The origin of the 10 to 15 year window quoted for gallbladder carcinogenesis, which is the argument that cholecystectomy for stones or dysplasia in high-incidence regions prevents cancer years later.
Similar pages
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Shares Intracholecystic papillary-tubular neoplasm (ICPN), Dysplasia (pre-cancerous change), Gallbladder cancer.
- Key paperSalmonella manipulation of host signaling pathways provokes cellular transformation associated with gallbladder carcinoma
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- TermCarcinoma in situ (CIS)
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- CancerCarcinoma in situ and dysplasia of the gallbladder
Shares Dysplasia (pre-cancerous change), Gallbladder cancer.