[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Gastrointestinal tract](https://durgical.com/en/general-pathology/areas/gi/) › Colorectal adenocarcinoma

# Colorectal adenocarcinoma

- Lesion

Colon cancer grows from polyps over years; right-sided ones bleed silently and cause anaemia, left-sided ones narrow the bowel.

Updated Nov 12, 2026

## Key points

- APC/β-catenin (chromosomal instability) pathway, up to four in five sporadic cancers: APC loss early, KRAS later, then SMAD2/4 and TP53 with chromosomal losses.
- Microsatellite instability pathway: mismatch-repair loss; TGFBR2 and BAX mutations; right side, mucinous, lymphocyte-rich; respond to checkpoint inhibitors.
- CpG island methylator (CIMP) pathway: MLH1 promoter methylation, BRAF mutation, from sessile serrated lesions; right side.
- Right-sided tumours: exophytic polypoid masses, rarely obstruct, present with iron deficiency anaemia and fatigue.
- Left-sided tumours: annular napkin-ring constrictions, change in bowel habit, visible bleeding, obstruction.
- Iron deficiency anaemia in an older man or a postmenopausal woman is gastrointestinal cancer until proven otherwise.

## 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)](https://durgical.com/en/conditions/colorectal-polyps-and-hereditary-polyposis-syndromes/) | APC, then KRAS, SMAD4, TP53; aneuploidy | Tubular or villous adenoma | Left or right; typical gland-forming adenocarcinoma |
| [Microsatellite instability (germline)](https://durgical.com/en/conditions/lynch-syndrome/) | MSH2 or MLH1 germline mutation; TGFBR2, BAX | Few adenomas (Lynch) | Right side, mucinous, lymphocytes; younger |
| [CIMP with MSI (sporadic)](https://durgical.com/en/conditions/colorectal-polyps-and-hereditary-polyposis-syndromes/) | 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.

## Memory aid

Right side: rich in blood loss and anaemia. Left side: left with a narrow napkin ring and obstruction.

## 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.

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## Connections

## Related 9

- [Colonic adenomas and serrated lesions](https://durgical.com/en/general-pathology/colonic-adenomas-and-serrated-lesions/)
- [Hereditary colorectal cancer: FAP and Lynch syndrome](https://durgical.com/en/general-pathology/hereditary-colorectal-cancer-fap-and-lynch-syndrome/)
- [Colitis-associated neoplasia: dysplasia in long-standing IBD](https://durgical.com/en/general-pathology/colitis-associated-neoplasia-dysplasia-in-long-standing-ibd/)
- [Metastases to the liver: the most common liver malignancy](https://durgical.com/en/general-pathology/metastases-to-the-liver-the-most-common-liver-malignancy/)
- [Multistep carcinogenesis: the adenoma–carcinoma sequence](https://durgical.com/en/general-pathology/multistep-carcinogenesis-the-adenoma-carcinoma-sequence/)
- [Grading and staging: what TNM means](https://durgical.com/en/general-pathology/grading-and-staging-what-tnm-means/)
- [Tumour markers: serum and tissue, and what each one is for](https://durgical.com/en/general-pathology/tumour-markers-serum-and-tissue-and-what-each-one-is-for/)
- [Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum](https://durgical.com/en/general-pathology/genomic-instability-mismatch-repair-brca-and-xeroderma-pigmentosum/)
- [Pathways of spread and the usual metastatic sites](https://durgical.com/en/general-pathology/pathways-of-spread-and-the-usual-metastatic-sites/)

## Related conditions 8

- [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/)
- [Colorectal polyps and hereditary polyposis syndromes (FAP, Lynch)](https://durgical.com/en/conditions/colorectal-polyps-and-hereditary-polyposis-syndromes/)
- [Lynch syndrome (hereditary non-polyposis colorectal cancer)](https://durgical.com/en/conditions/lynch-syndrome/)
- [Large bowel obstruction](https://durgical.com/en/conditions/large-bowel-obstruction/)
- [Iron deficiency anaemia](https://durgical.com/en/conditions/iron-deficiency-anaemia/)
- [Ulcerative colitis](https://durgical.com/en/conditions/ulcerative-colitis/)
- [Crohn disease](https://durgical.com/en/conditions/crohn-disease/)
- [Lower gastrointestinal bleeding](https://durgical.com/en/conditions/lower-gastrointestinal-bleeding/)

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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](https://www.cancer.gov/types/colorectal/patient/colon-treatment-pdq) (National Cancer Institute, 2025); [Colorectal Cancer Screening](https://www.ncbi.nlm.nih.gov/books/NBK559064/) (StatPearls (NCBI Bookshelf), 2025); [Colorectal cancer disparities in Latin America: Mortality trends 1990-2019 and a paradox association with human development](https://europepmc.org/article/PMC/PMC10456201/) (PloS one, 2023).

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Source: https://durgical.com/en/general-pathology/colorectal-adenocarcinoma/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/colorectal-adenocarcinoma/