Colorectal Cancer Flashcards
Which ones are oncogenes and which ones are tumor suppressor genes?
- p53
- DCC
- APC
- Kras
Which one is the most frequently mutated in CRC? What % of the time?
Which one of those have implications with cetuximab? What about chemo?
What is the order of mutation in adenocarinogenesis?
P53: tumor suppressor
DCC: tumor suppressor
APC: tumor suppressor
Kras: oncogene
Kras is the most common (50% of all colon cancer)
If Kras mutation (+) then you can’t give cetuximab. Chemo is also not as effective if there is a kras mutation
APC -> Kras -> p53
P53 mutation is correlated to higher or lower colorectal cancer survival rate?
How is the DCC mutation thought to be related to the metastatic potential?
DCC(+) tumors are correlated to higher or lower prognosis?
P53 mutation = lower survival rate
DCC product is important in cell-cell adhesions. Mutation thought to enhance metastatic potential.
DCC(+) = normal cell-cell adhesions = low metastasis, better prognosis
MSI-H vs. MSI-L
which one is more likely to be high grade?
Which one is more likely to be on the right side?
MSI tumors have a better or worse prognosis than microsatellite stable tumors?
MSI tumors have a better or worse response to chemotherapy?
MSI-H more likely to be high grade, more likely to be right side
MSI(+, either high or low) have better prognosis than microsatellite stable tumors
MS stable: more responsive to chemo
MSI: less responsive to chemo
Overall what % of CRC are hereditary vs environmental?
35% hereditary, 65% environmental
FAP
- autosomal dominant or recessive?
- gene is on what chromosome?
- what % is not genetic/no fam Hx?
- what # cutoff for attenuated vs full?
- cancer most definitely by what age?
- what is CHRPEs? Why does it matter?
- what % FAP pts have desmoids?
- autosomal dominant
- chromosome 5q21. APC
- 22% occur de novo
- <100 polyps = attenuated FAP
- cancer by age 40
- congenital hypertrophy of retinal pigmented epithelium. Not present in attenuated FAP
- 30%
- when and how frequently to start Colonoscopies for FAP?
- when to start EGDs on FAP?
- when to offer surgery for FAP?
- when do you start screening for Lynch syndrome? How frequent?
- what if adenoma found?
- 10-12.
- EGD at age 20
- if >1000 colonic polyps or >20 rectal polyps then ASAP. Otherwise between age 16-20. In females wait til maturity.
- known mutation: age 21 or 10 years younger than age of onset of affected relative. Whichever is younger. Also do pelvic exam annually starting age 25 for ovarian cancer.
- every 2 years until age 40 then yearly
- yearly if adenoma found
- post-op surveillance for FAP after IRA?
- IRA: Flex sig every 12 months
- IPAA: pouchoscopy yearly
MutYH associated polyposis
- autosomal dominant or recessive?
- when should you suspect this?
- what is the lifetime risk of CRC? when do you start screening?
- treatment?
- autosomal recessive
- test for this when you have someone who looks like FAP but tests negative for APC
- 70-80% lifetime risk. Start at age 20
- TAC with IRA
SMAD4
- what syndrome?
- lifetime risk of CRC?
- when to start Colonoscopies?
- treatment? When to do surgery?
SMAD4
- juvenile polyposis syndrome
- 50% lifetime risk
- start at age 12-15
- TAC with IRA. Surgery if high grade dysplasia or cancer or can’t manage polyps with endoscopy
STK1
- What syndrome?
- autosomal dominant or recessive?
- what do you need to screen?
- treatment?
- Peutz-Jegher
- autosomal dominant
- testicular exam, pap smear, mammogram, scope, CA19-9
- just remove the polyps. If cancer or high grade dysplasia or uncontrollable endoscopically then TAC with IRA.
PTEN
- what syndrome?
- what cancers?
- Screening colonoscopy?
- surgery?
- Cowden syndrome
- breast, thyroid, endometrial, CRC
- start in 30’s, every 3 years
- TAC, IRA when polyps can’t be controlled
HNPCC
- lifetime risk of cancer?
- lynch I vs Lynch II?
- colon cancer location preference?
- synchronous cancers?
- pathology?
- surgery?
- [T/F] If pt gets an adenoma in Lynch syndrome, they become cancer faster
- what genes?
- treatment?
- risk of rectal cancer?
- survival better or worse than sporadic when matched for age and stage?
- stage II & III with MSI. benefit of 5FU?
- MSI-H better or worse prognosis?
- 80% lifetime risk
- Lynch I: colorectal only. Lynch II: gastric, endometrial, ovarian, kidney etc
- proximal to splenic flexure.
- increased risk 7% vs 1% in Sporadic
- mucinous differentiation with signet rings
- TAC, IRA
- true. HNPCC polyps grow 1-3 years instead of the usual 10
- MLH1, MSH2 (higher risk for other cancers)
- Prophylactic TAC/IRA AND hysterectomy
- 12% risk of rectal cancer at 12 years after IRA
- survival is better than sporadic
- if microsatellite unstable, no benefit for 5FU
- MSI-H better prognosis
What are Amsterdam I Vs Amsterdam II?
Amsterdam I
- 3 histologically confirmed cancers in family
- 2 consecutive generations
- 1 dz before age 50
- 0 FAP
Amsterdam II
Amsterdam I + extracolonic cancers (ovarian, uterine, urothelial)
Colon cancer. What layer does it invade? T1 T2 T3 T4
T1: submucosa
T2: muscularis propria
T3: breaks through the muscularis propria into subserosa
T4: through the serosa
Incidence if lymph node met with
T3 rectal cancer?
30-50%
