13: Colorectal Cancer Flashcards
Explain the epidemiology of colorectal cancer
- 4th most common type of cancer
- 2nd leading cause of cancer death
- age: mainly 50-70/80
- diet + genetic risk factors
What is a polyp?
any projection from a mucosal surface into a hollow viscus, and can have many causes (e.g. m<be></be>
What is an adenoma?
An adenoma is a benign neoplasm of the mucosal epithelial cells
What are the characteristics of hyperplastic polyps in the colon?
- Very common
- <0.5 cm
- 90% of all LI polyps
- Often multiple
- Most: No malignant potential
- 15% have k-ras mutation
What are the different types of adenomas that can occur in the colon?
What are their differences?
- Tubular (>75% tubular)
- Normally Pedunculated –> harder to invade into submucosa and mucosa (has head, neck, stalk)
- Tubulovillous (25- 50% villous)
- mixed type)
- Villous ( > 50% villous)
- normally sessile –> easier to invade into submucosa and mucularis
Explain the microscopic structures of tubular adenomas
- Columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
- Increased proliferative activity
- Reduced differentiation
- Complexity/disorganisation of architecture
What are the microscopic changes and characteristics of villous adenomas?
- Mucinous cells with nuclear enlargement, elongation, multilayering and loss of polarity
- Exophytic, frond-like extensions –> finger like
- Rarely may have hypersecretory function and result in excess mucus discharge and hypokalemia
Explain the epidemiology of colonic adenomas and their potential to turn carcinomas
- 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)
- Likely to turn to carcinomas in 10years-15 years
- Cancers stay at a curable stage c. 2 years
What are the main genes involved in the adenoma carcinoma sequence of Colorectal cancer?
- APC,
- K ras,
- Smads (signal transducers of TGF-ß)
- p53,
- telomerase activation
What are microsattelites?
What is their role in the formation fo colorectal cancer?
Areas of repeated DNA sequences, more prone to mutation than other areas
- Encode form many proteins, e.g. of some TSG
- inhibit Growth and apoptosis
- mismatch gene repair
- –> Need 2 hits
What is HNPCC ?
Autosomal recessive condition that leads to imparied mitssmatch repair and therefore to increased microsattelite instability
–> Inherited high risk of cancer
Explain the adenoma-carcinoma sequence in the formation of Colorectal cancer
AK 53: 1: APC, 2nd K-ras, 3rd. P53
- First hit of TSG (can be inherited or or aquired)
- E.g. APC, MSH2 (missmatch repair)
- nothing happens
- 2nd hit of TSG
- APC, MSH2, ß-catenin
- nothing happens
- Protooncogene mutation
- e.g. K-Ras
- adenoma formation
- Homozygous loss of additional cancer supressor
- P53, LOH
- Carcinoma
- Irregulated control and loss of many genes
Why is APC Especially Important in Colon Cancer?
Because it is the gene that turns off ongoing proliferation in the crypts
–> in colon proliferation is needed all the time!
Explain the role of diet in the formation of colorectal cancer
It has a hugh influence. Increased risk if
- western diet (high temperature red meat)
- high fat
- low fibre
- refined carbohydrates
- Dietarey deficiencies
What is the clinical presentation of colorectal cancer?
Red flags:
- Change in bowel habit
- Bleeding PR
- Unexplained Iron deficiency anaemia
+
- Mucus PR
- Bloating
- Cramps (‘colic’)
- Constitutional (weight loss, fatigue)
What are the macroscopic features of Colorectal Cancer?
Small carcinomas may be present within larger polypoid adenomas, pedunculated or sessile
What is the distribution of colorectal carcinomals in the gut
What is the Dukes Classification?
A way of staging Colorectal carcinomas
A-C with increasing severity
- Dukes A - growth limited to mucosa/submucosa
- nodes negative
Dukes B - growth into or beyond muscpropria
- nodes negative
Dukes C1 - nodes positive
- apical LN negative
Dukes C2 - apical LN positive
