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%
Lymphatic drainage of tumor proximal to dentate line
Lymphatic drainage of tumor distal to dentate line
Proximal to dentate: IMA and internal iliac via middle and inferior rectal
Distal to dentate: femoral and inguinal
What is the definition of CRM and when is it considered threatened?
Circumferential resection margin
Closest distance of the tumor to the mesorectal fascia
Threatened when the tumor extends within 1mm or less of the mesorectal fascia.
For lower tumors, when they invade the intersphincteric plane
What is consolidation vs induction therapy?
Neoadjuvant systemic chemo given AFTER completion of chemoradiation/radiation therapy = “consolidation therapy”
“Induction chemotherapy” = systemic chemo delivered prior to neoadjuvant chemorad/radiation therapy
