Colorectal Carcinoma Flashcards
Majority type
Arise from
Specific mutations drive proliferation of mucosa to cancer
Adenocarcimoa
adenomatous polyps (only minority develop molecular changes to become cancer)
activating oncogenes, loss of tumor suppresors
CRC may also develop from
Epigenetic alterations
Hypermethylation phenotype
serrated polyps
hypermethylation of promotor region in mismatch repair enzymes (MLH1 and NSH2) red gene expression
CIMP+, sporadic CRC
Genetic mutations
APC TP53 TGFB$2 MLH1 MSH2 PTEN
A- tumor suppresor (cant degrade B-catenin)
TP53- tumor suppresor (loss of cell cycle reg)
TGFBR2- TS, loss of signal mediating arrest
M- DNA mismatch defect
P- oncogene, act PI3k
Adenomatous polyp gross appearance
Histology
greatest risk fo transformation
Predisposing factors
peducunlated/sessile
tubular/tubulovillous/villous
Villous/sessile
genetic syndromes, IBD, lifestyle
Familaial Ademomatous Polyposis (FAP)
Develops
Mutation in
Pattern
Requires
Presence of extraintestinal manifestations
highest rate of CRC
hundreds of polyps in adolesence, 1000 adenomas by 3rd decade
APC gene
AD
somatic mutation (2nd hit)
Gardner syndrome
Hereditary Nonpolyposis Colorectal Carcinoma (HNPCC)/ Lynch Sydnrome
Pattern
Defect
Microsatellites
In this dz
Presents, side
AD
mismatch repair genes (MLH1/MSH2/MSH6/PMS2)
short, repet DNA sec prone to mutations
microsat goes uncorrected, accumulates mut in onco/TS
earlier, R
Extracolon manifestations of HNPCC
MUYTH polposis
results in
Endometrial/Ovarian/Uro/SB/Gastric
AR pattern- mutation in BER MUT4H
100s of adenomas
IBD
inc risk over
pathway
Possible mutations
common develops CRC
decades
chronic inflamm- dysplasia
RAS onco, TP53
Dietary factor
effect of exercise
other factor
inc Fat/red meat/high calorie
inversely prop to CRC
smoking
CRC incidence highest in
lowest in
western countries (diet/lifestyle)
Africa/ C/S Asia
CM
R sided tumors
L sided cancers
Constipation presents w
Late in course
Asx for years
Occult blood
blood loss, Fe def anemia, fatigue
Const, obstruc
frequent, loose stools/bloody
palpable mass/metastasis (HSM)
Screening
Avg
Mod (1st rel w adenoma>60)
High risk (CRC<60, 2+ rel w CRC, ademoa <60)
FAP/HNPCC
IBD
start, interval
@ 50, or earlier w RF
50, 10
40, 10
40, 5
20, 1-2
10yrs after dx, 1-2
Gold standard screening
process
benefit
Probs
Flexible sigmoidoscopy
benefit
harm
Colonoscopy (use for high risk)
colonoscope from rectum to ICV
polypectomy
sedation, complete bowel prep, bleeding
smaller, rectum/D colon
can biopsy/prep
no polypectomy/
Fecal occult blood testing
detects
avoid using
Important consideration
Findings should be
Fecal Immunochemical Testing
3 sep stool samples, testing for occult blood
peroxidase activity of heme
Aspirin/NSAID 7 days, red meat 3 days prior
does not reliably detect adv adenomas
ABs for human Hb/albumin (better sensitibity)
CT colonography
Requirs
Fecal stool DNA (fsDNA)
also has high
radiographic- high false +, poor sensitivity
bowel prep, colonoscopy FU
PCR amplify for gene mutations- CRC sheds DNA in stool
FP
