Cancer as a Disease – Colorectal Cancer

Question 1

What type of carcinoma are most colon cancers?

Answer 1

Adenocarcinoma

Question 2

What is the rate of turnover of cells in the colon?

Answer 2

2-5 million cells per minute

Question 3

What is a polyp?

Answer 3

Any projection from a mucosal surface into a hollow viscus, may be hyperplastic, neoplastic, inflammatory

Question 4

What is an adenoma?

Answer 4

Benign neoplasm of the mucosal epithelial cells

Question 5

List 3 different types of colonic polyp

Answer 5

Metaplastic/hyperplastic
Adenoma
Lipoma

Question 6

State 4 characteristics of hyperplastic polyps.

Answer 6

VERY COMMON (90% of all colonic polyps)
< 0.5cm
NO malignant potential
15% have K-ras mutations

Question 7

What are the different types of colonic adenoma?

Answer 7

Tubular (majority)
Tubulovillous
Villous
The more villous it is the worse it is

Question 8

What are the different shapes of colonic adenomas?

Answer 8

Pedunculated: looks like a tree (more successful removal)
Sessile: looks like a hedge

Question 9

What is the difference between tubular and villous adenomas?

Answer 9

Tubular: COLUMNAR cells with nuclear enlargement, elongation, multi-layering, loss of polarity, increased proliferative activity, reduced differentiation + disorganisation of architecture
Villous: MUCINOUS cells with nuclear enlargement, elongation, multi-layering + loss of polarity. May be exophytic. May have hypersecretory function leading to hypokalaemia.

Question 10

What is the most famous condition that causes an increased number of colonic polyps?

Answer 10

Familial Adenomatous Polyposis

Question 11

What gene mutation is FAP caused by?

Answer 11

5q21

Question 12

What are the two genetic pathways in colorectal cancer?

Answer 12

Adenoma-carcinoma sequence = presence of adenomas will increase the risk of colorectal cancer (origin of most CRCs)
Microsatellite instability

Question 13

What are microsatellites?

Answer 13

Repeat sequences of DNA prone to misalignment
Some are found in coding sequences of genes which inhibit growth or are involved in apoptosis
If mismatch repair genes mutate, results in microsatellite instability, leads to CRC

Question 14

State two genetic diseases that predispose to colorectal cancer.

Answer 14

Familial adenomatous polyposis: inactivation of APC tumour suppressor gene
HNPCC: microsatellite instability (affects mismatch repair genes)

Question 15

State 4 dietary factors that can increase the risk of colorectal cancer.

Answer 15

High fat
Low fibre
High red meat
Refined carbohydrates

Question 16

State two dietary deficiencies that can increase the risk ofcolorectal cancer.

Answer 16

Folates: co-enzyme for nucleotide synthesis + DNA methylation
MTHFR: disruption of DNA synthesis + DNA instability (leads to mutation). Decreases methionine synthesis leading to genomic hypomethylation + focal hypermethylation (gene activating + silencing effects)

Question 17

What is the clinical presentation of colorectal cancer? (7)

Answer 17

Change in bowel habit  
PR bleeding  
Unexplained iron deficiency anaemia
PR mucus
Bloating 
Cramps/ Colic
Weight loss/ fatigue

Question 18

Describe the distribution of colorectal cancer.

Answer 18

RECTOSIGMOID: 55%
Caecum/Ascending: 22%
Transverse: 11%
Descending: 6%

Question 19

Describe the Dukes classification of colorectal cancers.

Answer 19

Dukes A
Growth limited to the wall (mucosa + submucosa) 
Nodes negative 
Dukes B  
Growth beyond muscularis propria 
Nodes negative 
Dukes C1 
Nodes positive 
Apical nodes negative 
Dukes C2  
Apical nodes positive

Question 20

State 3 clinical features that diminish the prognosis of colorectal cancer.

Answer 20

Bowel obstruction/ perforation
Age < 30
Distant metastases

Question 21

State 5 pathological features that affect the prognosis of colorectal cancer.

Answer 21

Degree of differentiation
Depth of bowel wall penetration  
Number of regional lymph nodes involved  
Venous invasion  
Lymphatic invasion

Question 22

What are the criteria for a screening programme?

Answer 22

Condition should be important with respect to the seriousness +/or frequency
Natural history of the disease must be known in order to: Identify where screening can take place
To enable effects of any intervention to be assessed

Question 23

What are 4 characteristics of a screening test?

Answer 23

Simple + acceptable to patient
Sensitive + selective
Cost effective
Screening population should have equal access to the screening procedure

Question 24

What does the NHS colorectal cancer screening look for?

Answer 24

Faecal occult blood (FOB)
If positive + 55-60 years = sigmoidoscopy
If positive + >60 years = full colonoscopy

Question 25

State the 6 layers of the colonic wall

Answer 25

Mucosa: Epithelium + Lamina propria
Muscularis mucosa
Submucosa
Muscularis propria
Serosa
Mesenteric fat

Question 26

What characteristic of cell lifespan in the colon renders it vulnerable to mutation? What natural mechanisms do we have to eliminate mutated cells?

Answer 26

High cell turnover- more likely mutation will occur
Natural loss (sloughed off at top of villus)
DNA monitors
Repair enzymes

Question 27

What is the function of APC? Why does dysfunctional APC cause cancer?

Answer 27

APC holds B catenin in inactive state in cytoplasm

Mutated APC doesn’t bind B catenin, so B catenin moves into nucleus, increases cell proliferation

Question 28

How does colorectal cancer incidence change with age?

Answer 28

Increases with age

Question 29

What pathological feature can improve prognosis of colorectal cancer?

Answer 29

Local inflammation + immunologic reaction

Question 30

What features indicate high risk for colonic cancer?

Answer 30

Previous adenoma
1st degree relative affected by CRC <45
IBD
Hereditable cancer families