Colon cancer

Question 1

How does sporadic adenocarcinoma of the colon present?

Answer 1

Malaise, weakness, weight loss, altered bowel habits, anaemia and obstruction of lumen on colonoscopy

Question 2

What do pathological samples show?

Answer 2

Mucin secretions, fibrostroma, irregular glands and large nuclei.

Question 3

How is colon carcinoma treated?

Answer 3

Hemicolectomy

Question 4

What is a polyp?

Answer 4

A preneoplastic lesion that forms cancer

Question 5

What staging is used for colon cancer?

Answer 5

Duke’s classification - describes the spread and invasion through the layers of the colon.

Question 6

What are the stages of Duke?

Answer 6

A - Confined to bowel wall
B - Spread beyond muscle to serosa
C - Lymph node involvement
D - Highest nodal involvement

Question 7

What is the histology of colon cancer?

Answer 7

Poorly differentiated with lymphovascular and perineural invasion.

Question 8

What are the prognostic factors of colon cancer?

Answer 8

Microsatellite stability - chromosomal instability due to allelic loses, amplification, translocations, mutations of APC, KRAS and TP53
Microsatellite instability - Inactivation of MMR genes that normally play a role in repairing genes when damaged

Question 9

What is MMR? How are the normally lost?

Answer 9

Mismatch repair genes.
Usually lost in pairs so loss of protein.
Concern of MMR if had multiple colonic tumours at a young age.

Question 10

What is the sporadic cause of colon cancer?

Answer 10

Loss of MLH1 and mutated BRAF - less aggressive and don’t metastasis to lymph. Mostly associated with cancer of proximal colon.

Question 11

What is the germline cause of colon cancer?

Answer 11

Lynch syndrome - autosomal dominant germline mutation in MMR gene that causes early presentation of cancer in the right colon and other peritoneal structures

Question 12

Which genes are lost in Lynch syndrome?

Answer 12

MSH2 and MSH6
MLH1
Should test whole family for the genes and pt needs to be monitored for other types of cancers.

Question 13

What is the role of Ras in colorectal tumours?

Answer 13

Somatic Ras gene mutations in 45% of tumours. Mutation causes constitutive activation of protein. Pt with this mutation are unlikely to benefit from treatment with anti-EGFR Igs.

Question 14

What role does BRAF play in colorectal caner?

Answer 14

BRAF mutation has poor prognosis and cannot use anti-EGFR therapy

Question 15

Why is Ras status important?

Answer 15

Must be known before treatment is started as Panitumumab is contraindicated with chemo in pts with mutant Ras.

Question 16

How does UC predispose?

Answer 16

Ulcerative colitis has low grade dysplasia that can develop into cancer. It affects the rectum and proceeds proximal. It produces a moderately differentiated cancer with lymph and vascular invasion.