Dysplasia Carcinoma Sequence in Colorectal Cancer Flashcards
What patients are most at risk of colorectal cancer?
Middle aged to elderly patients with a diet high in red meat and low in folate who are more sedentary and have high body weight
What are adenomatous polyps?
precursor lesions for colorectal carcinoma
What features of a polyp predict whether it will become cancer?
size, villous morphology, high grade dysplasia
What are two familial syndromes which can lead to early onset colorectal cancer?
Lynch syndrome and familial adenomatous polyposis (FAP)
What percentage of colorectal cancers is due to Lynch syndrome?
3%
What percentage of colorectal cancers is due to FAP?
1%
What diseases may predispose the patient to early onset colorectal cancer?
inflammatory bowel diseases like ulcerative colitis and crohn’s disease
What gene mutation is there in FAP?
APC gene mutation
What is the syndrome of FAP?
more than 100 adenomatous polyps in the large bowel
What is the treatment for FAP?
total colectomy
What does an adenomatous polyp look like histologically?
abnormal crypt architecture, crowded cells, enlarged and hyper chromatic nuclei, goblet cell depletion, increased mitotic cells, does not invade beyond the muscularis mucosae
What defines a colorectal adenocarcinoma?
When there is invasion beyond the muscularis mucosae and a desmoplastic stromal reaction
What are three genetic pathways leading to colorectal cancer?
chromosomal instability, microsatellite instability, CpG island methylator phenotype
What genetic instability causes Lynch syndrome?
microsatellite instability
What genetic instability causes FAP?
chromosomal instability
Which proto-oncogenes are commonly mutated in colorectal cancer?
K-RAS and B-RAF
Which tumour suppressor genes are commonly mutated in colorectal cancer?
SMAD4/SMAD2 and p53
What is a sessile serrated polyp?
a polyp in the more proximal colon that is more difficult to detect in a colonoscopy
What are the macroscopic features of colorectal cancer?
typically firm and white, may be necrotic, may be mucoid, may be stenosing if in distal colon
What is the typical presentation for an ulcerated colorectal tumour?
Anemia
How is colorectal cancer staged according to the ACPS system?
A- invades muscularis mucosae
B- invades muscularis propria
C- lymph node metastases
D- distant metastases
Why is EGFR targeted therapy ineffective for K-RAS and B-RAF mutations?
Because it blocks signalling upstream of ras and raf
