Colorectal Cancer Flashcards
Describe the epidemiology of Colorectal cancer
Major Cancer in ‘developed’ countries
4th most common cancer overall
2 leading cause of cancer death overall, behind lung cancer
What is the function of the colon
Extraction of water from faeces (electrolyte balance)
Faecal reservoir (evolutionary advantage)
Bacterial digestion for vitamins (e.g. B and K)
Describe the micro anatomy of the colon
Crypts of Lieberkuhn
Made up of columnar, goblet and endocrine cells + STEM cells. Surrounded by ECM and mesenchymal cells
Describe the turnover of the colon
2-5 million cells die every minute in the colon and these are replaced
Proliferation renders cells vulnerable (e.g. APC mutation prevents cell loss mutation)
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
benign neoplasm of the mucosal epithelial cells
What are the types of polyp
Hyperplastic / metaplastic Adenomas Juvenile Peutz Jeghers Lipomas
Describe the hyperplastic polyp
Benign 90% of all colonic polyps <0.5cm Cells well ordered (see right) Multiple polyps often present No malignant potential
What type of cell can a colonic adenoma contain
tubular or villous (or tubulovillous if mixed)
Describe the protrusion of colonic adenomas
pedunculated or sessile
Which types of cell are sessile adenomas usually made up of
sessile ones tend to be more villous
Describe tubular ademonas
Tubular adenomas are the most common type
Comprise columnar cells showing signs of dysplasia
What are the signs of dysplasia
Nuclear enlargement Multilayering Loss of polarity Increased proliferation Decreased differentiation Architectural disorganisation
Describe villous adenomas
Comprise mucinous cells also showing the signs of dysplasia, with exophytic, frond-like extensions.
In rare cases they can be hypersecretory and lead to hypokalaemia.
Explain how ulcerative colitis affects colorectal cancer risk
Causes increased proliferation in an attempt to repair damage, and the inflammation also damages the basement membrane, making invasion easier. Thus, UC causes a higher risk of colorectal cancer.
What can be done to reduce risk of cancer
Remove any polyps
Describe the adenoma-carcinoma sequence
- Germline or somatic mutations of cancer suppressor genes (first hit)
- Methylation abnormalities, inactivation of normal alleles (second hit)
- Protooncogene mutation
- Homozygous loss of additional cancer suppressor genes
- Additional mutations
- Gross chromosome alterations
What are the 2 main ways in which genetic predisposition to colon cancer can occur
familial adenomatous polyposis (FAP)
hereditary non-polyposis colorectal cancer (HNPCC)
How does familial adenomatous polyposis lead to genetic disposition to colon cancer
inactivation of APC tumour suppressor genes.
How does hereditary non-polyposis colorectal cancer lead to genetic disposition to colon cancer
Due to microsatellite instability
Microsatellites are repeat sequences prone to misalignment, often mismatch repair genes.
Describe the major clinical presentation of colorectal cancer
Change in bowel habit (more/less constipated, going more frequently, anything) Bleeding PR (per rectum) Iron deficient anaemia otherwise unexplained
What are the potential clinical presentations of colorectal cancer
Mucus PR
Bloating
Cramps (‘colic’)
Weight loss, fatigue, etc.
Describe the distribution of colon cancer
Most colorectal cancers occur in the sigmoid colon or rectum, the rest distributed fairly evenly.
Since malignancy often develops from dysplasia, you can find small carcinomas
present within larger polyps.
What proportion of colorectal cancers are moderately differentiated
70%
10% well
20% poorly
Describe Dukes A
growth limited to wall (muscularis propria); nodes negative
Describe Dukes B
growth beyond muscularis propria; nodes negative
Describe Dukes C1
nodes positive; apical lymph node negative
Describe Dukes C2
apical lymph node positive
What features suggest that patients are at high-risk for colorectal cancer (and are screened)
Had a previous adenoma
A close relative affected by colorectal cancer <45yo
2 close relatives affected by colorectal cancer at all
Evidence of a dominant familial cancer trait
Ulcerative colitis or Crohn’s disease
Define population screening
the practice of investigating apparently healthy individuals with the object of detecting unrecognised disease or a high risk of developing disease, and of intervening in ways that will prevent the occurrence of disease or improve the prognosis when it develops
