Colorectal adenocarcinoma
- Lesion
Colon cancer grows from polyps over years; right-sided ones bleed silently and cause anaemia, left-sided ones narrow the bowel.
What it is
Colorectal adenocarcinoma is the commonest malignancy of the gut and causes nearly a tenth of cancer deaths worldwide. It peaks at sixty to seventy, though early-onset cases are rising. Diet low in fibre and high in refined carbohydrate and fat, obesity and inactivity raise risk; aspirin and NSAIDs lower it, perhaps through COX-2 inhibition. Three molecular pathways explain most tumours. Depth of invasion and lymph-node metastasis are the strongest prognostic factors, and the liver is the commonest site of distant spread.
Structure
- Most tumours: tall columnar cells resembling adenoma epithelium, forming glands within desmoplastic stroma (firm consistency).
- Some poorly differentiated tumours form few glands; mucinous tumours pool mucin in the wall and carry a worse prognosis; rare signet-ring tumours.
- Spread: regional nodes, liver (portal drainage), lungs and bone; distal rectal and anal cancers can bypass the liver.
Step by step
- Both APC alleles are lost in colonic epithelium: β-catenin enters the nucleus with TCF.
- MYC and cyclin D1 drive proliferation: a small adenoma.
- KRAS activation enlarges the adenoma.
- Loss of SMAD2 or SMAD4 frees cells from TGF-β growth arrest.
- TP53 loss and chromosomal instability allow invasive carcinoma.
- Telomerase and further changes support metastasis.
The three molecular pathways
| Pathway | Key changes | Precursor | Typical tumour |
|---|---|---|---|
| APC/β-catenin (CIN) | APC, then KRAS, SMAD4, TP53; aneuploidy | Tubular or villous adenoma | Left or right; typical gland-forming adenocarcinoma |
| Microsatellite instability (germline) | MSH2 or MLH1 germline mutation; TGFBR2, BAX | Few adenomas (Lynch) | Right side, mucinous, lymphocytes; younger |
| CIMP with MSI (sporadic) | MLH1 methylation, BRAF mutation | Sessile serrated lesion | Right side, mucinous; older |
Markers
- CEA (follow-up, not screening)
- Mismatch-repair proteins (MLH1, PMS2, MSH2, MSH6)
- KRAS, NRAS, BRAF status
- CK20+, CK7−, CDX2+
Clinical notes
- TNM staging builds on the old Dukes system: depth of invasion (T), nodes (N), distant metastasis (M).
- Colorectal cancer mortality is rising in many Latin American countries as diets and lifestyles change.
- Mismatch-repair testing guides genetic counselling and immunotherapy.
Test yourself
Think of the answer, then tap the question to see it.
What is the usual first genetic event in the classic adenoma–carcinoma sequence?
Loss of both copies of APC, which allows β-catenin to accumulate and activate Wnt target genes.
Why do right-sided colon cancers present with anaemia rather than obstruction?
They grow as exophytic masses in the wide caecum and ascending colon and bleed occultly; left-sided tumours are annular and narrow the lumen.
Which features mark microsatellite-unstable colon cancers?
Right-sided location, mucinous differentiation, abundant tumour-infiltrating lymphocytes and loss of mismatch-repair proteins.
What is the most common site of distant metastasis of colorectal cancer, and why?
The liver, because the colon drains through the portal circulation.
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Colon Cancer Treatment (PDQ®)–Patient Version (National Cancer Institute, 2025); Colorectal Cancer Screening (StatPearls (NCBI Bookshelf), 2025); Colorectal cancer disparities in Latin America: Mortality trends 1990-2019 and a paradox association with human development (PloS one, 2023).
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Representative model, for educational purposes only.