Cancer as a Disease – Colorectal Cancer Flashcards
What type of carcinoma are most colon cancers?
- Adenocarcinoma
What is a polyp?
- Any projection from a mucosal surface into a hollow viscus
What is an adenoma?
- Benign neoplasm of the mucosal epithelial cells
What are the different types of colonic polyp?
- Metaplastic/hyperplastic
- Adenoma
- Juvenile
- Peutz-Jegher
- Lipomas
State some characteristics of hyperplastic polyps
- These are VERY COMMON 90% of all colonic polyps
- They have NO malignant potential
- 15% have K-ras mutations
What are the different types of colonic adenoma?
- Tubular
- Tubulovillous
- Villous
- NOTE: the more villous it is the worse it is
What are the different shapes of colonic adenomas?
- Pedunculated – looks like a tree
- Sessile – looks like a hedge
What is the difference between tubular and villous adenomas?
- Tubular– COLUMNAR cells with nuclear enlargement, elongation, multi-layering and loss of polarity + increased proliferative activity + reduced differentiation
- Villous– MUCINOUS cells with nuclear enlargement, elongation, multi-layering and loss of polarity. May be exophytic
Describe dysplasia, and what are the 3 stages of dysplasia?
- Abnormal growth of cells with some features of cancer for example……
- Disorganisation including pseudostratification where unexpected, hyperchromatic nuclei with a high nuclear : cytoplasmic ratio
- Indefinite
- Low grade
- High grade
What is the most famous condition that causes an increased number of colonic polyps?
- Familial Adenomatous Polyposis
What gene mutation is FAP caused by?
- Mutation in 5q21 - APC mutation
What do adenomas often progress into?
- Often progress into carcinomas
What are the two genetic pathways in colorectal cancer?
- Adenoma-carcinoma sequence = presence of adenomas will increase the risk of colorectal cancer
- Microsatellite instability
What are microsatellites?
- Repeat sequences of DNA that are prone to misalignment
- Some microsatellites are found in coding sequences of genes which inhibit growth or are involved in apoptosis
Describe adenoma-carcinoma progression
- Dysplastic cells in adenoma
- There is accumulation of damage to the DNA leading to loss of control of proliferation
- The cells become invasive as well
State two genetic diseases that predispose to colorectal cancer
- Familial adenomatous polyposis – inactivation of the APC tumour suppressor gene
- Hereditary Nonpolyposis Colorectal Cancer (HNPCC or Lynch syndrome) – microsatellite instability (affects mismatch repair genes)
State some dietary factors that can increase the risk of colorectal cancer - i.e. things that are bad in the diet - not in regards deficiencies
- High fat
- Low fibre
- High red meat
- Refined carbohydrates
State two dietary deficiencies that can increase the risk of colorectal cancer and how they increase the risk
- Folates– important for nucleotide synthesis and DNA methylation
- MTHFR
- Deficiency leads to disruption of DNA synthesis and DNA instability (this leads to mutation)
- It also causes decreased methionine synthesis leading to genomic hypomethylation and focal hypermethylation – this can have gene activating and silencing effects
Give 4 anti-cancer elements in food and how they work to have anti-cancer benefits
- Vitamin C: ROS scavenger - scavenges free radicals that would otherwise damage DNA
- Vitamin E: ROS scavenger - scavenges free radicals that would otherwise damage DNA
- Isothiocyanates (found in cruciferous vegetables)
- Polyphenols (green tea, fruit juice) - activate MAPK
What is the clinical presentation of colorectal cancer?
- Change in bowel habit
- PR bleeding
- Unexplained iron deficiency anaemia
Describe the distribution of colorectal cancer
- RECTOSIGMOID –55%
- Caecum/Ascending –22%
- Transverse –11%
- Descending –6%
What are the 3 subtypes of adenocarcinoma in colorectal cancer?
- Mucinous carcinoma
- Signet ring cell
- Neuroendocrine
Describe the Dukes classification of colorectal cancers
DUKES A
- Growth is limited to the wall (muscularis propria)
- Nodes negative
DUKES B
- Growth beyond the muscularis propria
- Nodes negative
DUKES C1
- Nodes positive
- Apical nodes negative
DUKES C2
- Apical nodes positive
State some clinical features that affect the prognosis of colorectal cancer
- Bowel obstruction (diminished prognosis)
- Age < 30 (diminished prognosis)
- Distant metastases (diminished prognosis)
State some pathological features that affect the prognosis of colorectal cancer
- Depth of bowel wall penetration
- Number of regional lymph nodes involved
- Venous invasion
- Lymphatic invasion
What are the criteria for a screening programme?
- Condition should be important with respect to the seriousness and/or frequency
- The natural history of the disease must be known in order to:
- Identify where screening can take place
- To enable the effects of any intervention to be assessed
What are the characteristics of a screening test?
- Simple and acceptable to the patient
- Sensitive and selective
- Cost effective
- Screening population should have equal access to the screening procedure
What does the NHS colorectal cancer screening look for?
- Faecal occult blood (FOB)
- If positive and 55-60 years = sigmoidoscopy
- If positive and over 60 years = full colonoscopy
