Colorectal Cancer Flashcards
What are adenomatous polyps?
Precursor lesions for colorectal carcinoma (can be tubular or villous, pedunculated or sessile)
What is the risk of early onset colorectal cancer with FAP?
100%
What increases the risk of early onset colorectal cancer?
Familial syndromes (e.g. FAP, HNPCC/Lynch syndrome) Chronic inflammatory bowel disease (more commonly UC)
What gene is mutated in FAP?
APC
How is FAP inherited?
AD
How is FAP treated?
Prophylactic colectomy (curative because the polyps do not invade past the muscular mucosa, and there are no lymphatics in the lamina propria so no opportunity for spread)
Describe the histological features of an adenomatous polyp in FAP
Abnormal crypt architecture
Dysplasia (crowded cells with abnormal nuclei, goblet cell depletion, increased or atypical mitoses)
No invasion past muscularis mucosa
What are the 3 main colorectal cancer genetic pathways?
Chromosomal instability Microsatellite instability (MSI) CpG island methylator phenotype (CIMP)
What is HNPCC?
Hereditary nonpolyposis colorectal cancer (aka Lynch syndrome)
What is the role of APC loss in the dysplasia-carcinoma sequence for colorectal cancer?
Decreased cell adhesion
Increased cell proliferation
What are the most common accumulated mutations in colorectal cancer?
Proto-oncogenes: K-RAS, B-RAF
TSGs: SMAD4/SMAD2, p53
Activation of telomerase
Describe the multi-step model for colorectal cancer
Normal epithelium FIRST HIT APC MUTATION (somatic or familial) B-CATENIN MUTATION Dysplastic ACF Early adenoma K-RAS MUTATION Intermediate adenoma SMAD4 MUTATION Late adenoma p52 MUTATION Carcinoma OTHER ALTERATIONS Metastasis
What is the most common familial colorectal cancer syndrome?
HNPCC
How is HNPCC inherited?
AD
What gene is mutated in HNPCC?
DNA mismatch repair gene (MSI)
What genetic changes occur in the MSI pathway for colorectal cancer?
Defective DNA mismatch repair due to germline mutation of MSH2 or MLH1
Widespread mutations in DNA microsatellites leads to mutations in wide range of other genes
Where do sessile serrated adenomas generally arise?
Proximal colon
What histological features are seen in sessile serrated adenomas?
Saw-tooth architecture Complex branching "Boot-leg" angulation and dilation at base of crypts Cytological changes Increased atypia with dysplasia
What mutation is commonly seen in sessile serrated adenomas?
B-RAF (may be precursor to MSI or CIMP)
What staging system is used for colorectal cancers and what classifications are there?
Australian ClinicoPathological Staging (ACPS):
A - invades beyond muscularis mucosa
B - invades beyond muscularis propria/externa
C - LN metastases
D - distant metastases
N.B. Used in combination with TNM
What is a common site of metastasis for colorectal cancer? Why?
Liver, because portal vein drains the gut
What targeted therapies exist for colorectal cancer?
Ab-based therapies that block EGFR signalling
Cetuximab
EGFR inhibitor
Panitumumab
EGFR inhibitor
