Colorectal Cancer Flashcards
What cancer is the major cancer of the developed world?
Colorectal cancer
- Environmental (diet) and genetic factors in aetiology
3 main functions of the colon
- Extraction of water from faeces
(electrolyte balance) - Faecal reservoir
- Bacterial digestion for vitamins (e.g. B and K)
What type of carcinoma are most colon cancers?
Adenocarcinoma
What is the rate of turnover of cells in the colon?
2-5 million cells per minute
What is a polyp?
Any projection from a mucosal surface into a hollow viscus, and may be hyperplastic, neoplastic, inflammatory, hamartomatous, etc.
What is an adenoma (of the colon)?
An adenoma is a benign neoplasm of the mucosal epithelial cells
What are the different types of colonic polyp?
Metaplastic/hyperplastic
Adenoma
State some characteristics of hyperplastic polyps.
- VERY COMMON (90% of all colonic polyps)
- They have NO malignant potential
- 15% have K-ras mutations
What are the different types of colonic adenoma?
- Tubular
- Tubulovillous
- Villous
NOTE: the more villous it is the worse it is
What are the different shapes of colonic adenomas?
Pedunculated – Adenomas on a stalk (looks like a tree)
Sessile – Flat and raised adenoma (looks like a hedge)
Describe the microscopic structure of tubular adenomas
- Columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
- Increased proliferative activity
- Reduced differentiation
- Complexity/disorganisation of architecture
Describe the microscopic structure of villous adenomas
- Mucinous cells with nuclear enlargement, elongation, multilayering and loss of polarity
- Exophytic
- Rarely may have hypersecretory function and result in excess mucus discharge
Where is the gene mutation that causes familial adenomaous polyposis (FAP aka APC) caused by?
Many patients with the mutation have what?
5q21 (Site of mutation determines clinical variants)
Many patients have prophylactic colectomy
25% of adults have adenomas at age 50. What does the adenoma usually progress into? How do decrease the incidence of this progression?
Most carcinomas arise from adenomas
Endoscopic removal of polyps decreases the incidence.
What are the two genetic pathways in colorectal cancer?
Adenoma-carcinoma sequence
Microsatellite instability
What are microsatellites?
Repeat sequences of DNA that are prone to misalignment
Some microsatellites are found in coding sequences of genes which inhibit growth or are involved in apoptosis
State two genetic diseases that predispose to colorectal cancer.
Familial adenomatous polyposis – inactivation of the APC tumour suppressor gene
HNPCC – microsatellite instability (affects mismatch repair genes)
State some dietary factors that can increase the risk of colorectal cancer.
High fat
Low fibre
High red meat
Refined carbohydrates
State two dietary deficiencies that can increase the risk of colorectal cancer.
Folates:
Folates are co-enzymes needed for nucleotide synthesis and DNA methylation.
MTHFR – Methylenetetrahydrofolate Reductase:
- Deficiency leads to disruption in DNA synthesis causing DNA instability and mutation.
- Decreased methionine synthesis leads to genomic hypomethylation and focal hypermethylation à gene activating and silencing effects.
What is the clinical presentation of colorectal cancer?
Change in bowel habit
Pre-Rectal bleeding
Unexplained iron deficiency anaemia
Describe the distribution of colorectal cancer.
Half of all cancers will occur in the rectosigmoid area, the remainder are distributed throughout the colon
Describe the Dukes classification of colorectal cancers.
Dukes A -Growth is limited to the mucosa/submucosa - Nodes negative Dukes B - Growth beyond the muscularis propria (into serosa) - Nodes negative Dukes C1 - Nodes positive - Apical nodes negative Dukes C2 - Apical nodes positive
How do tumours occurring in the caecum and right colon present typically, and why?
Tumours occurring in the caecum and right colon often present later and with vaguer symptoms, partly due to the capacity of the caecum to expand before getting blocked
Diagnosis of colon cancer?
Diagnosis is usually by a combination of radiology, but particularly endoscopy.
As yet, there are no reliable markers of colorectal cancer than can be measured in the blood.
