CRC

Question 1

what are the main types of polyps?

what are some concerning macroscopic findings

Answer 1

villous are the worst of the adenomas (dysplastic)

serrated polyps (previously considered benign but info evolving

high risk features:

large > 1cm

severe dysplasia

multiple polyps

sessile or flat

villous architecture

Question 2

what are some of the mutations that can lead to CRC? (when accounting for the change from an adenoma)

Answer 2

usually the first is APC or 5qLOH

then K-ras

then multiple other

see image

Question 3

what is the microsatellite instability associated with non-familial CRC?

Answer 3

the MLH1 is the most common.

interestingly, MSI actually makes the cancer more chemoresponsive

the presence of heavy methylation of tumour suppressor genes

Question 4

there are two pathways for CRC

what are the names of them? and what is the one associated with BRAF?

Answer 4

it is called the MAPK signalling pathway and it is associated with serrated neoplasm pathway (note there are adenomas and serrated polyps)

Question 5

what are the levels of the australian clinicopathological system for CRC?

Answer 5

a - limted to mucosa, not through the muscularis propria - 5 yr survival 85%

b - through the mus propria - 5 year survival 70-80%

c- LN mets 5 yr survival 40-60%

d - distant mets or irresectable local disease - 5 years <5%

Question 6

what is teh colonscopy surveillance when someone has a CRC?

Answer 6

an initial colonoscopy to make sure there’s no synchronous CA

then 1 year

then 3 year

if normal, back to 5 yearly

Question 7

what is the role for CEA in CRC?

Answer 7

there isn’t any role in diagnosis or screening

it may be useful to monitor for recurrent disease

Question 8

is there any difference between treatment of colonic and rectal CA?

Answer 8

there is higher rates of local recurrence in rectal CA

adjuvant therapy should include XRT because of this

this is the only of the CRC where rtx applies

Question 9

how often should people with two relatives on the same side of the family under age 55 get screening

Answer 9

every 5 years get a scope, starting at age 50 OR 10 years before youngest diagnosis

Question 10

how often should people with a single affected first degree relo over 55 years be screened?

Answer 10

as per the standard over 50 population

FOBT?

flexi sig every 5 years

Question 11

what is the genetic abnormality see in FAP?

is there any other locations of polyps?

Answer 11

this is an auto dominant mutation in the APC tumour suppressor gene

but about 30% is de novo

patients also suffer duodenal polyps

Question 12

what is Peutz-Jaeger syndrome?

what cancers do they have increased risk of?

Answer 12

these are polyps, that are particularly associated with small intestine

there is inc risk of GI cancer, panc, breast, testicular, ovarian cancer

it is an autosomal dominant condition

Question 14

what is Lynch syndrome?

Answer 14

this is an autosomal dominant mutation in the mismatch repair gene, often MSH2, MLH1 or MSH6

often RIGHT SIDED (proximal colon) with multiple primary cancers

we confirm the diagnosis by testing for MSI from the cancer

but it’s actually easier to examine the excised cancer for loss of expression of hMLH1, hMSH2 and MSH6 and PMS2 - this is the more common test

Question 15

how do we differentiate between sporadic MSI (microsatellite instabilty) and Lynch?

Answer 15

the sporadic should have gone through a multi-hit process and as such, will also have BRAF oncogene mutation too

Question 16

what is the screening of Lynch syndrome?

Answer 16

starting at age 25,

yearly, or at worst, 2nd yearly colonoscopies