bowel cancer: pathology and screening process Flashcards
why use the term bowel cancer
public understanding
devised following survey following screening programme
only applies to large intestine
how common is bowel cancer
1/3 most common cancer in women and men (breast/prostate and lung)
high incidence in west, low in Asia and central africa
affects men and women equally
why does bowel cancer occur
environmental disease- preventable
migrating to high risk area inc risk eg Japan to USA study
red meat and fatinc
veg, fruit anf fibre dec by inc faecal bulk and reduce transit time
physical activity and low BMI - low risk
risk factors for bowel cancer
inc
red meat and fat
UC, crohn’s (lesser), adenoma in LB, prev history of bowel cancer surgery, FH, old age
veg, fruit anf fibre dec by inc faecal bulk and reduce transit time
physical activity and low BMI - low risk
how does a high fibre diet reduce bowel cancer
inc formation of short chain FAs promoting healthy gut micro-organism and reduce proliferation of neoplastic cells
inc stool bulk to reduce transit time so carcinogens have less contact with mucosa
high fibre diet stops secondary bile acids, potentially carcinogenic
what is a polyp
protruding growth into a hollow viscus can be being, adenoma or malignant
in bowel cancer its either innocent or precancerous
if polypoid, not called polyp, just cancer
what are most polyps in the LB
adenomas (precancerous lesions consisting of dysplastic epithelium)
diagnosis can only be confirmed on microscopic exam by pathologist
what is dysplasia
cells have morphological features of cancer but without invading surrounding tissue
low grade - early precancerous features
high grade- advanced precancerous with high risk of invasion
what are the pathological features of polyps
hyperplastic - numerous goblet cells, lace like patterns
tubular adenoma - test tube like appearance
villous adenoma - finger like
tubovillous adenoma - mix of tubular and villous features
what is the adenoma-carcinoma sequence
stepwise progression from normal mucosa to adenoma to cancer
morphological features also mirrored at genetic level where there are stepwise alterations
carcinoma of bowel example
what is the evidence of adenoma-carcinoma sequence
observation studies have shown sporadic cancer not genetically determined but arising from adenomas
shown by
pops high prevalence of adenoma - high prevalence of cancer
diet of adenomas in LB mirrors that of bowel cancer (eg 60% both arise from left colon and rectum)
peak incidence of polyps predates cancer dev
residual adenoma found
risk of cancer related to amount of polyps
remove adenomas ad reduce risk of cancer
what is the genetic basis of the adenoma-carcinoma sequence
familial adenomatous polyposis (FAP) min of 100 polyps in LB, usually have 500-2500 dysplastic so adenomas 100% risk of cancer by 30 prophylactic colectomy at 20 cont to 1% bowel cancer
genetics of FAP in bowel cancer
hereditary autosomal dominant
defective gene of Chronic 5q21 (APC gene)
get 1st abnormal gene in utero
2nd genetic abnormality in somatic cells
dev polyps young (need 2nd hit to dev)
two hit hypothesis in hereditary and sporadic bowel cancer
FAP born with first hit and acquires 2nd hit after birth to develop adenomas then cancer
in sporadic cancer, two hits in somatic cells = a then c
Knudosn to explain hereditary retinoblastoma
what does the 2nd hit result in
loss of heterozygosity (2 abnormal genes)
mutation of APC gene important to initiate BC
2nd hit - homozygous for cancer
acquire more genetic abnormalities to progress with AC seq
what is the stepwise progression from adenoma to cancer
inherited or acquired mutation 1st high
hyperproliferative epithelium - methylation abnormalities 2nd hit
early A - mutation K-RAS
int A and late A- lose TSGs
invasive cancer - telomerase activity for immortality
genetic abnormalities associated with bowel cancer
Lynch syndrome/HNPCC FAP attenuated FAP (<100 adenomas) familial colorectal cancer type X MUTYH associated polyposis serrated polyposis syndrome hamartomatous polyposis syndrome
what is Lynch syndrome
familial cancer affecting caecum and right colon before 50
ass with endometrial, SB, UT cancer
2-3% BC
no precursor polyps
BC young pts to advanced cancer tested for Lynch routinely
what are the genetics of Lynch syndrome
different from FAP
during replication DNA BPs mismatch
no repairs - errors accumulate - microsatellites (tandem repeat of nucleotides in DNA, fixed for life)
expansion and contraction of repair nucleotides (=MS instability)
as FAP inherit 1st and acquire 2nd
what genes are linked to LS and cancer
routinely test for MSH2, MLH1, PMSI and PMS2
how is LS assessed
Amsterdam criteria
>3 relatives with LS related cancer (LB, SB, UT, endomet)
1 affected should be 1st deg relative of other 2
>2 successive gens
>1 diagnosed before 50
FAP excluded
tumour verified pathologically
symptoms of bowel cancer
can be asymptomatic
change in bowel habit (constipation and diarrhoea from obstruction)
bleeding from rectum
anaemia (esp caecum due to slow occult blood loss)
abdo pain from obstruction
how is bowel cancer diagnosed
history and examination flexible sigmoidoscopy and colonoscopy with biopsy and histo exam CT colonography (if no colonoscopy) staging CT MRI for rectal cancer (local spread)
what is the pathology of bowel cancer
graded as well, mod and poorly differentiated
well diff - normal mucosa
mod - most common
poor - minimal of no glandular differentiation
how is bowel cancer staged
T- tumour, depth of invasion of bowel wall
N - lymph node metastasis
M - distant metastasis to liver or lung
bowel wall is mucosa to end of ext muscularis propria
what are the types of T staging
T1 - invasion of submucosa, muscularis propria clear
T2 - muscularis propria but not full thickness invasion
T3 - full thickness bowel wall, nit serosa
T4 - present on serosa
how is cancer N staged
Lymph node metastasis
eg Tn N1
how is cancer T staged
liver metastasis M1
Tn Nn Mn
what is bowel cancer screening
looking for early signs in healthy people
prevent cancer by detecting polyps precancer
curable stage
methods for BCS
stool test or faecal immunochemical test (FIT)
Flex sigmoidoscopy (FS) (detects polyps and cancers in rectum and left colon)
Colonoscopy ideal but needs expert and sedation
in UK FS at 55, FIT from 60-74 yrs (2years)
what is Stool Testing and FIT
test for occult blood
FIT Ab-antigen reaction to Ab in blood
+ve doesn’t = BC
haemorrhoids and inflammation can cause +ve
what is the science behind the stool test
Ulcerating cancers bleed silently
trauma to large polyps due to friction with stool can bleed
get stool kit, do test in home, sent to lab and processed by machine
what happens with a positive stool test
referred for colonoscopy to detect polyps, early cancer and advanced cancer
FIT doesn’t detect non-bleeding polyps or cancer, repeated every two years
