Colorectal cancer Flashcards
Colorectal cancer epidemiology
- major cancer in developed countries
- 4th most common cancer worldwide
- 2nd leading cause of cancer death overall (behind lung cancer)
- aetiology includes environmental factors (diet) and genetic factors
Colon function
- Extraction of water from faeces (electrolyte balance)
- Faecal reservoir (evolutionary advantage)
- Bacterial digestion for vitamins (eg: B and K)
Colonic anatomy
-smooth folded mucosa with thick muscle layer
Turnover of colon cells
- 2.5 million cells die per minute in colon=high proliferation rate
- proliferation renders cells vulnerable to mutation
- APC mutation prevents cell loss
Normal protective mechanisms to eliminate genetically defective cells:
- natural loss
- DNA monitors
- repair enzymes
Polyp
- any projection from a mucosal surface into a hollow viscus
- may be hyperplastic, neoplastic, inflammatory, hamartomatous etc
Adenoma
-benign neoplasm of mucosal epithelial cells
Colonic polyp types
- metaplastic/ hyperplastic
- adenomas
- juvenile
- Peutz Jeghers
- lipomas
- others (essentially any circumscribed intramucosal lesions)
Hyperplastic polyps
- very common growth
- <0.5cm
- constitute 90% of all colon polyps
- often come in multiples
- no malignant potential
- 15% have K-Ras mutation
Colonic adenoma types
- Tubular (>75% tubular)
- Tubulovillous (25-50% villous)
- Villous (>50% villous)
- Flat
- Serrated
Colonic adenoma anatomy
- adenomas on a stalk=pedunculated
- flat and raised adenoma=sessile
Microscopic structure of adenomas (tubular)
- columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
- increased proliferative activity
- reduced differentiation
- complexity/ disorganisation of architecture
Microscopic structure of adenomas (villous)
- mucinous cells with nuclear enlargement, elongation, multilayering and loss of polarity
- exophytic, frond-like extensions
- rarely may have hypersecretory function resulting in excess mucus discharge and hypokalemia
Dysplasia
- abnormal growth of cells with some features of cancer
- subjective analysis
- given indefinite, low grade and high grade classification
Adenomatous Polyposis Coli (APC/FAP)
- 5q21 gene mutation
- site of mutation determines clinical variants (eg: classical, attenuated, Gardner, Turcot etc)
- many patients have a prophylactic colectomy
Colonic adenoma
- 25% of adults have adenomas at age 50=5% of these become cancers if left
- large polyps have higher risk of becoming cancerous than smaller polyps
- cancers stay at curable stage for about 2 years
Progression from adenoma to carcinoma
- most colorectal carcinomas arise from adenoma with 10-30% of colorectal carcinomas having a residual adenoma
- adenomas and carcinomas have a similar distribution
- adenomas typically precede cancers by 15 years
- endoscopic polyp removal decreases incidence of subsequent colorectal carcinomas
Dysplasia associated lesion
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Adenoma carcinoma sequence
-APC, K ras, Smads, p53, telomerase activation
Microsatellite instability
- microsatellites=repeat sequences prone to misalignment
- some microsatellites are in coding gene sequences which inhibit growth or apoptosis
- mismatch repair genes (MSH2) are recessive and require 2 hits for loss
Genetic predisposition to colorectal cancer
1) FAP=inactivation of APC TSG
2) HNPCC=microsatellite instability