GI neoplasms 2 Flashcards
How many polpys must be prsent to dx FAP?
Inheritance pattern?
Gene affected?
need 100
autosomal dominant
APC germile gene on 5q (but 25% sporadic)
Where are the adenomas in FAP? what do you do for these pts?
most are in the colon, can be anywhere and require a prophylactic colectomy bc 100% cance of developing colon adenocarcinoma
FAP
age of onset of polyps
Age of onset of CRC
Age of onset: median = 16 years, range from 5-38 w/ increasing # detected with age. Cancer at late 30s
Varients: Attenuated FAP <100 polpys; usually on the ___ terminus while classic is at the ___
C
N
adenomatous polyposis w/ osteomas, epidermoid cysts, desmoid tumors
Gardners syndrome: variatn of FAP
: adenomatous polyposis with medulloblastoma
Turcot; variant of FAP
hereditary colorectal cancer syndrome; phenotypic overlap with FAP; mostly attenuated FAP, 20-100 adenomatous polyps; but can have more then 100
MYH Associated Polyposis (MAP)
Inheritance pattern of MAP
Mutation of MAP
Age presenation of pts
Auto- recessive
mutated MYH gene: 1p34.3-p32.1
Present older then FAP
Define the role of teh MYH protein
DNA repair protein; base excision repair; takes our A—G mismatch
494A—> G
1145G—> A
are two common mutations
Increased risk of colorectal cancer and extra-intestinal cancer; endometrial cancer in females (w/ sm.inets/ureter/renal pelvis)
Lynch sydnrome: Herediary nonpolyposis Colorectal cancer
What is the age of onset for adenoma in Lynch compared to other syndromes?
Adenomas occur earlier then normal but in low #s::: Colonic carcinoma IG occurs in mulitples, not ass. w/ adenomas
What is the defect responsible for Lynch sydrome?
defect often DNA mismatch repair: microsatelilite instability pathway
Features of Lynch:
accelerated carcinogeneis (adenoma—> carcioma) in _____ yrs vs 8-10
see____ CRC pts have Lynch syndrome, risk for second primary cancer is 16% in 10 yrs
2 to 3
1/35
How do first degree relatives of Lynch patients do?
risk for new cancer in first/second degree relative = 35-45% by age 70 but better survival rate bc most are associated with increased inflammation thus boosts host immune response to cancer
assoicated w/ lots of sebaceous adenomas, sebaceous carcinomas and keratoacanthomas; ie SKIN cancers with sebaceous adenomas
Muir-Torre syndrome:
part of LYNCH!!!
Lifetime risk of following cancers if you have MMR gene mutation
colon, male:
Colon, female:
Endometrium:
Sm intestine:
stomach
ovarian
colon, male: 28-50%
Colon, female: 24-50%
Endometrial: 30-50%
Sm intestine: 4-7%
stomach: 2-13%
ovarian: 3-13%
Describe key histology in Lynch syndrome
Mucinous features and chronic inflammation with signet ring features
What are my MMR or mismatch repair genes?
MSH1 and MSH2 recognize and fix shit
PMS2 and MSH6
MSH2/MSH6 will:
identify the mismatch
MSH1/PMS2 will
fix the mismatch
*see loss of MMR funtion sporadic (___%) or hereditary (__%) leading to accumulation of mutations
12
3
Staining is:
MLH1: +
PMS2: +
MSH2: +
MSH6: +
likely sporadic cancer
Staining is:
MLH1: -
PMS2: -
MSH2: +
MSH6: +
LS or sporadic
MLH1 mucation or MLH1 hyperpigmentation
Staining is:
MLH1: +
PMS2: +
MSH2: -
MSH6: -
Mutation is likely LS:
MSH2 mutation
