Colorectal cancer Flashcards
five symptoms of colorectal
occult or overt rectal bleeding change in bowel habits pain and discomfort in bowel weakness/fatigue weight loss
inside to outside of colonic histology (and what it’s made of)
mucosa (epithelial goblet cells making crypts and lamina propria)
muscularis mucosa (thin muscle layer aids peristalsis)
submucosa (dense irregular connective tissue, vasculature and nerves)
MUSCULARIS EXTERNA made up of:
- inner circle
- outer longitudinal
Serosa (intraperitoneal lining)
TNM staging pT (extent of local invasion)
pT0 - no evidence of primary tumour pT1 - tumour invades submucosa pT2 - tumour invades muscularis propria pT3 - invades into subserosa pT4 - tumour perforates visceral peritoneum (4a) and/or directly invades other organs
What is grade
differentation - architecture and specifically gland formation (how close does it resemble a normal gland)
Other prognostic factors than grade/staging
tumour deposits
venous invasion
lymphatic invasion
perineural invasion
colorectal cancer usually arises from what
a polyp (10-15y) origin cell: stem cell in base of crypt
what are the two major pathways to neoplastic disease
- adenoma to carcinoma (chromosomal instability)
2. serrated neoplasia sequence (microsatellite stable/instable)
specific risk factors for CRC (4)
age >50
polyps in colon (tubulovillous adenoma)
family history <10% (FAP, HNPCC)
ulcerative colitis
red flags for CRC
change in bowel habits per rectal bleed iron deficiency anaemia weight loss/appetite family history
investigations
colonscopy
CT colonogram
bowel screening programme
who is offered bowel screening
every 2 years to M/W aged 60-74
25 y/o woman with persistent diarrhoea and rectal bleed. which investigation would you do?
flexible sigmoidoscopy
55 y/o with Hx of painless jaundice for 4 weeks. which investigation?
abdo USS
two main types of genetic colorectal cancer
familial adenomatous polypopsis
hereditary nonolyposis colon cancer (HNPCC or Lynch)
FAP
hereditary
features
autosomal dominant
large number of polyps 100+ developing from adolescence. 90% have pigmented lesions in retina (CHRPE)
what’s the gene defect in FAP?
adenomatous polyposis coli (APC) gene on chrom 5.
nonsense or frameshift mutation
how to test for gene defect in FAP
protein truncation test
direct sequencing
APC is a tumour suppressor gene. what does it normally do
bind beta catenin
bind microtubules
what is beta catenin
a transcription factor usually present at low levels. when a cell wants to prolif, it synthesises lots of it. stimulates genes that promote cell division
when not needed - degraded by APC
APC keeps levels of beta-cat low.
why do apc defects affect the colon
normally Wnt pignalling is inactive halfway up the villus
when defect - activated all the way up - cells don’t know where they are. disordered signalling
extra-intestinal involvement of FAP CRC
masses of benign tumours jaw cysts sebaceous cysts osteomata pigmented lesions of the retina (CHRPE)
Features of HPNCC/lynch syndrome
low number of polyps
can be underlying cause of other tumours (endometrium, ovarian, small intes, stomach)
what do the defective genes in HNPCC mutations have in common
they all recognise when DNA bases haven’t been matched up properly (mismatch repair genes)
either involved in recognising the mismatch or cutting away section for repair
what regions are more susceptible to errors in DNA base matching
repetitive regions (microsatellite instability)
