Cancer 13: Cancer as a disease - Colorectal cancer Flashcards
What parts of the colon can become cancer?
Caecum, ascending, transverse, descending anf sigmoid
Describe colonic anatomy
See slides
Describe the turnover of the cells of the colon?
- 2-5 million cells die per minute in the colon!
Proliferation renders cells vulnerable - the greater the rate of proliferation the greater the chance of a mutation or error. - APC mutation prevents cell loss mutation
- Normally we have protective mechanisms to eliminate genetically defective cells by;
1) Natural loss
2) DNA monitors
3) Repair enzymes
Define polyps?
A polyp is any projection from a mucosal surface into a hollow viscus, and may be hyperplastic, neoplastic, inflammatory, hamartomatous, etc
Define an adenoma?
An adenoma is a benign neoplasm of the mucosal epithelial cells
What are the different types of colonic polyps?
Metaplastic/Hyperplastic Adenomas Juvenile Peutz Jeghers Lipomas Others (essentially any circumscribed intramucosal lesions)
What is a hyperplastic polyp?
See slides
Very common <0.5 cm 90% of all LI polyps Often multiple No malignant potential 15% have k-ras mutation
What are the different colonic adenoma types?
Tubular (rolls of testtubes) (>75%tubular) 90%
Tubulovillous (25- 50% villous) 10%
Villous (Vila like projections) ( > 50% villous)
(Flat)
(Serrated)
What is pedunculated and cecile adeomas?
See slides
pedunculated - Tree
Cecile - Lush rug
Describe the microstructures of tubular adenomas?
Columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
Increased proliferative activity
Reduced differentiation
Complexity/disorganisation of architecture
hyperchromatic nuclei
Describe the microstructures of villous adenomas?
Mucinous cells with nuclear enlargement, elongation, multilayering and loss of polarity
Exophytic, frond-like extensions
Rarely may have hypersecretory function and result in excess mucus discharge and hypokalemia
What is dysplasia?
Literal meaning ‘bad growth’. Abnormal growth of cells with some features of cancer
Subjective analysis:
Indefinite, low grade and high grade
What is APC/FAP?
Adenomatous Polyposis Coli
- 5q21 gene mutation
- Site of mutation determines clinical variants (classic, attenuated, Gardner, Turcot etc)*
- Many patients have prophylactic colectomy<30
Describe colonic adenomas?
25% of adults have adenomas at age 50
5% of these become cancers if left
Large polyps have higher risk than small ones (so 5% > 1 cm 50-60, 15% at 75)
Lead time 10 years - remove the polyp reduces the risk of cancer.
Cancers stay at a curable stage c. 2 years
Describe the progression from adenoma to carcinoma?
- Most CRCs arise from adenomas
- Residual adenoma in ~ 10-30% of CRCs
- Adenomas and Ca similar distribution
- Adenomas usually precede cancer by 15 years
- Endoscopic removal of polyps decreases the incidence of subsequent CRC
