Neoplastic Disease of Colon (GIT)

Question 1

Risk factors of bowel cancer?

Answer 1

Family history/genetic
Obesity
Diet high in processed meat and red meat
Alcohol
Inflammatory bowel disease, especially UC

Question 2

What are the 3 mechanisms of genetic instability that contribute to formation of colon cancer?

Answer 2

1. Chromosomal instability (high levels of DNA gains/losses/deletions)
2. Microsatellite instability (MSI) - due to defective DNA mismatch repair (MMR), elading to high mutation rate due to failed DNA repair mechanisms
3. Defective DNA polymerase proofreading (VERYhigh mutation rate as DNA polymerase can’t proof read DNA)

Question 3

Histological signs of dysplasia?

Answer 3

Large, hyperchromatic, irregular nuclei.

Fused glands

Loss of villi

Question 4

In what circumstances can dysplasia occur in the GIT?

Answer 4

Chronic inflammation

Neoplasms.

Question 5

What is the difference between an adenoma in teh GIT and adenomas elsewhere in the body?

Answer 5

Adenoma in GIT = pre-malignant potential.

Elsewhere in the body, adenomas generally do not become malignant.

Question 6

What are serrated adenomas?

What is the hallmark mutation involved in progression to carcinoma?

Answer 6

Colorectal neoplasms with serrated glands.

Pathway to carcinoma specifically involving the BRAF mutation.

Question 7

Three types of serrated polyps and their general features

Answer 7

Hyperplastic polyp - small, sessile or flat lesion. Serrated glands in superficial part of crypt.

Sessile serrated lesion - Serrated glands in full depth of crypt.

Serrated adenoma - larger, serrated epithelium showing dysplasia

Question 8

What are adenomatous polyps?

Are they benign / malignant / maligant-potential?

What determines prognosis/treatment

Answer 8

Adenomatous polyps are neoplasms with dysplastic glands.

Size determines risk - smaller ones can be removed endoscopically.

They are benign, but can progress to cancer through WNT mutations.

Question 9

Which condition means you’ll get colon cancer 100% of the time by age 40?

What gene is mutated?

Answer 9

FAP - Familial Adenomatous Polyposis

APC gene mutation (5q12)

Question 10

Mutation in MLH1 or MSH2 genes result in what syndrome and what kind of genetic instability mechanism?

Answer 10

Lynch syndrome - mismatch repair gene mutations = MSI instability.

Question 11

Which results in more polyps - familial adenomatous polyposis or lynch syndrome?

Answer 11

FAP = 100s of polyps.

Lynch = 10-20 polyps, but still more than sporadic cancer.