Colorectal Polyps
There are broadly two pathways toward colorectal malignancy, see here.
1. Adenoma-carcinoma pathway
- These can be sessile or peduculated.
- The molecular pathway develops through chromosomal instability (CIN) and involves loss of heterzygosity (loss of function of one allele). This leads to a progressive accumulation of mutations in tumour suppressors like APC, p53, and oncogenes like KRAS.
- Adenomatous polyps lead to microsattelite stable tumours.
- Commonly in the right colon more than the left.
2. Serrated Neoplasia pathway
- Includes hyperplastic polyps (traditionally no malignant potential), sessile serrated polyp, and traditional serrated adenoma.
- HP polyps are common and predominantly in the rectosigmoid junction.
- In contrast to the CIN pathway, serrated pathway is characterised by methylation of CpG islands in the promoter region of specific genes. Central to this pathway is progressive methylation and mutation in the BRAF oncogene, activating cell proliferation and leading to a sessile serrated polyp. A key step to dysplasia is the silencing of the mismatch repair gene hMLH1. This can rapidly become a microsatellite-unstable colorectal cancer.
3. Associated Notes