Cancer - colorectal
Description
- Adenocarcinoma in >95%
- Colon vs rectum are different diseases - rectal disease needs MRI, neoadjuvant therapy and a different surgical plan
Three molecular pathways
| Pathway | % | Mechanism | Features |
|---|---|---|---|
| Chromosomal instability | ~85% | APC -> KRAS -> TP53 (adenoma-carcinoma) | Left-sided, classic polyp sequence |
| Microsatellite instability (dMMR) | ~15% | MMR loss (germline Lynch, or somatic MLH1 hypermethylation) | Right-sided, mucinous, TILs, poorly differentiated |
| CpG island methylator (CIMP) / serrated | overlaps | BRAF V600E, sessile serrated lesions | Right-sided, elderly, F>M |
Sidedness matters therapeutically
| Right (proximal) | Left (distal) + rectum | |
|---|---|---|
| Molecular | BRAF, MSI-H, CIMP | RAS, chromosomal instability |
| Presentation | Anaemia, weight loss, mass; late | Obstruction, PR bleed, change in habit |
| Prognosis (metastatic) | Worse | Better |
| Anti-EGFR benefit | Minimal - do not use | Best |
MSI-H phenotype
- Proximal colon, large bulky local tumour, synchronous tumours more often
- Rarely metastasises distantly - stage-for-stage better prognosis
- Bimodal age: <50 (Lynch) or elderly (sporadic MLH1 methylation)
- Exquisitely immunotherapy-sensitive
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