Week 11 - Colorectal Cancer Flashcards
1
Q
What are adenomas?
A
- also called polyps
- gentle precursor wound
- for most cancers
2
Q
How is sporadic CRC screened?
A
- Fecal Occult Blood Test (FOBT)
- test for blood in stool
- flexible sigmoidoscopy
- rectum and sigmoid colon visually inspected
- where most cancers arise from
- detects 65-75% of polyps
- not all due to whole bowel not visualised
- 40-65% of CRCs
3
Q
What is the difference between benign and malignant tumours?
A
- benign
- slow growing
- well differentiated cells
- confined to normal location
- good forecast (prognosis)
- malignant
- faster
- poorer differentiation
- surrounding tissues
- distant secondary growth (metastasis)
- poor prognosis
4
Q
What genetic instabilities can cause sporadic CRC?
A
- Chromosomal INstability (CIN)
- chromosome number imbalance
- re-arrangement
- results in gene deletion (of APC tumour suppressor gene) and amplification
- Microsatellite INstability (MSI)
- changes in repeat numbers
- mutations in gene coding sequences
- loss of mismatch repair genes
5
Q
How can polyps be identified?
A
- colonoscopy
- removed to prevent cancer progressions
- earlier stages
- population based screening programme
6
Q
How is FAP caused?
A
- inherit single mutant APC allele
- acquire 2nd hit over time
- autosomal dominant
- 100% penetrant
- 100% CRC risk
7
Q
How does APC mutation cause CRC?
A
- also common in sporadic CRC
- activates Wnt signalling pathway
- β-catenin usually complexes with APC, axin and GSK3-β
- becomes phosphorylated
- targeted for degradation
- WNT target genes are not transcribed
- APC mutation causes β-catenin to uncouple
- cytoplasmic accumulation
- nucleus translocation
- complex with Lef/Tcf transcription factors
- activate target oncogenes e.g. cMYC and cyclin D1
- occurs in stem cells
- passed to daughter cells
8
Q
How can inherited CRC be differentiated from sporadic?
A
- early onset
- family history
- inherited in a mendelian manner
- rare cancers
- precursor lesions
- ethnicity
9
Q
What are the advantages of MSI testing?
A
- effective
- 93% sensitivity
- little tissue required
- highly reproducible
10
Q
What are the limitations of MSI testing?
A
- cannot be detected with lack of DNA
- does not identify mutated gene
11
Q
How does IHC screen for Lynch syndrome?
A
- ImmunoHistoChemistry
- determines if MMR proteins are absent in cancer tissues
- indicates possible mutation
- for genetic testing
- thin tissue section with antibody for each protein
- identify protein as brown stain
- under microscope
