Colorectal cancer Flashcards
Explain the molecular pathogenesis of colorectal carcinoma
- Enormous turnover of colonic epithelial cells
- High rate of proliferation makes cells vulnerable
- APC gene product reduces risk of mistakes during replication
- APC gene mutation (5q21) leads to hyperproliferation of the epithelium
- K-ras (oncogene) mutation combined with hypomethylation of DNA leads to formation of adenoma
- Mutation of p53 leads to development of a carcinoma
- Smads and p53, loss of heterozygosity and telomerase activation - cancer
Explain the major pathological features of colorectal carcinoma
- Larger lesion
- Tubular adenoma w/nuclei enlarged to irregular ovoid pattern w/thick, irregular nuclear membranes and increased no. of mitotic figures
- Also glandular structure becomes more complicated w/buds + branches + greater degree of irregularity
AND INVASION (penetration of muscularis mucoasae) - Ulcerative colitis can lead to dysplasia
- Increased no. of polyps (FAP)
Explain the clinical presentation of colorectal carcinoma
- CHANGE IN BOWEL HABIT bc colon extracts water from faeces
- RECTAL BLEEDING
- Tiredness and malaise due to UNEXPLAINED IRON DEFICIENCY ANAEMIA bc colon involved in bacterial digestion for vitamins (e.g. B, K)
- Mucus discharge
- Bloating
- Intermittent abdominal pain (colicky)
- Constitutional (weight loss, fatigue)
Majority are rectosigmoid
Macroscopic feature - small carcinomas may be present within larger polypoid adenomas (pedunculated or sessile)
Who is regarded as at high risk for colorectal carcinoma?
- Previous adenoma
- FD relative affected by colorectal cancer before 45
- 2 affected FD relatives
- Evidence of dominant familial cancer trait including colorectal, uterine, and other cancers
- UC, CD
- Hereditable cancer families (include other sites)
What are the principles of the adenoma-carcinoma sequence?
- Progression of adenomas to carcinomas is accompanied by an increasing degree of genetic abnormalities
- Clues to progression came from careful study of patients with hereditary colorectal cancers and comparing them to the patients with sporadic colorectal carcinomas
- Some early and some later events
- In general, the accumulation of mutations is more important than any specific order in which order they occur
- Main genes affected include APC, mismatch repair genes, P53, K-RAS, DCC (deleted in colorectal cancer), SMAD (loss) and E cadherin mutation
Define colorectal carcinoma staging systems
Dukes classification:
A - growth limited to the wall (muscularis propria), nodes negative
B - growth beyond muscularis propria, nodes negative
C1 - nodes POSITIVE, apical LN negative
C2 - apical LN POSITIVE
TNM classification
What is involved in NHS screening for colorectal carcinoma?
Look for faecal occult blood (FOB)
- If blood present –> endoscopy
- 55-60 yrs –> sigmoidoscopy
- 60+ –> full colonoscopy
- Look for adenomas that can be removed, but in some people they will find cancer
What is a polyp?
Any projection from a mucosal surface into a hollow viscus, and may be hyperplastic, neoplastic, inflammatory, hamartomatous etc.
Discuss familial adenomatous polyposis (FAP)
- Increases the number of polyps (1000s)
- 5q21 gene mutation
- Site of mutation determines clinical variants (classic, attenuated, Gardner, Turcot etc.)
- Many patients have prophylactic colectomy
- Link between APC and colon cancer allowed discovery of adenoma-carcinoma sequence
What is an adenoma?
Benign (but slightly disordered) neoplasm of mucosal epithelial cells –> increased cancer risk
Dysplastic but haven’t invaded through basement membrane
What are the major colonic adenoma types?
Tubular
Tubulovillous
Villous
What does the type of colonic adenoma tell you about how dangerous the adenoma is?
More villous = worse
What are the different shapes of adenomas?
Pedunculated - on a stalk, like tree
Sessile - flat and raised
Who is screened for colorectal carcinoma in the UK?
All women and men aged 60-74 - FOB every 2 years
Bowel scope screening for all women and men aged 55
