A3- Colorectal Cancer

Question 1

Malignant neoplasm of the colon or rectum, usually an __________

Answer 1

Malignant neoplasm of the colon or rectum, usually an adenocarcinoma.

Question 2

Is colorectal cancer the 1st 2nd or 3rd most common cancer in the UK

Answer 2

Third

Question 3

Colorectal cancer is commoner with advancing age

TURE OR FALSE

Answer 3

TRUE

Question 4

Colonic carcinoma affects men and women equally; rectal cancer appears
to be more common in women

TURE OR FALSE

Answer 4

FALSE

Colonic carcinoma affects men and women equally; rectal cancer appears
to be more common in men

Question 5

Which •Inflammatory bowel disease can cause colorectal cancer

Answer 5

ulcerative colitis

Question 6

nherited gene mutations conditons that relate to colorectal cancer?

Answer 6

FAP and lynch

Question 7

How does colorectal cancer present?

Answer 7

Change in bowel habit
•Constipation/diarrhoea
•Mucus
•Bleeding
•Intestinal obstruction
•Intestinal perforation

• Jaundice
• Abdominal distension
• Anaemia
• Anorexia (loss of appetite)
• Weight loss

Question 8

Difference in Right and Left Sided Colon Cancers

Answer 8

Right sided tumour: Polypoid carcinoma Symptoms: Blood loss,Weight loss

Left sided tumour:Stricturingcarcinoma Symptoms: Altered bowel habit, Obstruction, Rectal Bleeding

Question 9

Investigation Co Ca

Answer 9

• Simple blood tests
• FBC
• CEA

•Sigmoidoscopy or colonoscopy and tissue biopsy

Question 10

Difference between grade and stage?

Answer 10

• Grade –how similar to normal tissue the tumour appears under the microscope
• Stage –how far the tumour has spread

Question 11

Explain curative and palliative management for Colorectal Ca

Answer 11

•Curative
•Surgery +/‐adjuvant therapy
•Neo‐adjuvant therapy and subsequent surgery
•Palliative
•Chemotherapy
•Radiotherapy

Question 12

What is a somatic mutation

Answer 12

•Alteration in DNA that occurs after conception

Question 13

Hallmarks of cancer?

Answer 13

Question 14

What is meant by clonal evolution of cancer?

Answer 14

The clonal evolution model holds that genetic and epigenetic changes occur over time in individual cancer cells, and that if such changes confer a selective advantage they will allow individual clones of cancer cells to out-compete other clones.

Clonal evolution involves the interplay of selectively advantageous or ‘driver’ lesions, selectively neutral or ‘passenger’ lesions, and deleterious lesions, as well as lesions that increase the rate of other genetic changes

Question 15

Explain the different hit targets in clonal evolution

Answer 15

1st oncogenic mutation:
•stem cell/progenitor/differentiated cell
•growth of genetically homogeneous benign lesion

2nd hit targets one of the cells in the benign lesion
•growth of a more malignant and invasive clone

3rd hit targets cell within the malignant subclone
•further transformation
•genetically independent subclonescan coexist within tumour

Final mutational hit
•tumour entirely taken over by cells that behave as cancer stem cells

Question 16

Cancer of colon and rectum relatively well understood at ______ mutation
level

Answer 16

point

Question 17

Vogelstein’s adenoma‐carcinoma sequence in 1990

What did they measure?

Answer 17

His group measured the frequency of mutations in adenomas and
carcinomas and suggested a model for how a typical colorectal cancer
might develop

Question 18

•APC

Answer 18

• Tumour suppressor gene
• Point mutation creates a truncated protein
• Loss of function
• Considered initiation step in pathway

Question 19

RAS

Answer 19

•KRAS, NRAS oncogenes
•Encode GTP binding protein involved in signalling pathway from tyrosine kinase
pathway (MAPK pathway)
•Mutation prevents intrinsic GTPaseactivation
•Gain of function

Question 20

•p53

Answer 20

•DNA damage results in p53 mediated arrest in G1 phase of cell cycle
•This allows either DNA repair or p53 induced apoptosis
•Loss of function leads to accumulated mutations, continued cell proliferation and
decreased apoptosis

Question 21

What is DNA Mismatch Repair

Answer 21

System for recognising and repairing incorrect insertion, deletion and mis‐
incorporation of bases in DNA replication
•Defects in MMR increase the spontaneous mutation rate

Question 22

What is Microsatellite Instability (MSI)

Answer 22

Microsatellite instability (MSI) is a unique molecular alteration and hyper-mutable phenotype, which is the result of a defective DNA mismatch repair (MMR) system, and can be defined as the presence of alternate sized repetitive DNA sequences which are not present in the corresponding germ line DNA.

Question 23

•Microsatellite means

Answer 23

• Sequence (motif) of 1 to 5 nucleotides repeated between 10 –100 times
• E.g. AAAAAAAA, TTTTTTTT

•Prone to mutation during replication due to transient separation of the helical
strands and slippage of DNA polymerase complex

Question 24

RAS Mutation and its Consequences

Answer 24

RAS mutation
•Protein turned on all the time
•Blocking EGFR is not effective because the activation point in the pathway
is “downstream”

Question 25

NICE guidance is that all colorectal cancers should be tested for _____ _______

Answer 25

NICE guidance is that all colorectal cancers should be tested for Lynch Syndrome

Question 26

How is MMR Tested?

Answer 26

•Immunohistochemistry for expression of the four MMR protein in FFPE tumour
tissue
•If the protein is not expressed, there is loss of staining in the tumour tissue and
maintained staining in normal (control) tissue

• Immunohistochemistry (IHC) is generally preferred to MSI testing of the tumour
• Simpler
• Cheaper
• Can be offered in most pathology laboratories

Question 27

Benefits of MMR Testing

Answer 27

Finding cases of Lynch Syndrome
•Germline mutation in MMR proteins
•Reduces morbidity and mortality
•Identify relatives with disease

Finding sporadic MSI‐H colorectal cancers
•Approximately 10‐15%
•Known to have a better prognosis –no need for adjuvant therapy in most cases
•Potential for treatment with PD1 inhibitors