cancer 13 Flashcards
what does the colon do?
- Extraction of water from faeces
- Faecal reservoir
- Bacterial digestion for vitamins
describe the anatomy of the colon?
- The mucosa is folded but it is smooth
- There is a thick muscle layer (muscular)
- the cells of the colon are divided into crypts where the stem cells are found , they are then shunted up to the top of the villus where they are shed
what kind of cancers are colon cancers?
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what is the rate of turnover of cells in the colon?
- 2-5m cells per minute die in the colon -> high proliferation rate
what does APC normally do?
what does the APC mutation do to the cells?
- the gene product of APC reduces the risk of mistakes during replication
- APC mutation prevents cell loss and causes cell proliferation
what are the normal protective mechanisms of the cells of the gut?
- natural loss
- DNA monitors
- repair enzymes.
what is a polyp?
- any projection from a mucosal surface into a hollow viscus, and maybe hyperplastic, neoplastic, inflammatory, hamartomatous.
what are the types of colonic polyps?
-they can be :
- Metaplastic/hyperplastic
- Adenomas - Juvenile, Peutz Jeghers, lipomas (less common)
define adenoma:
benign neoplasm of the mucosa.
what are hyperplastic polyps?
how common are they?
how many have mutations?
- very common growths
- Constitute 90% of all colon polyps
- there are often multiple
- they have no malignant potential
- 15% has a K- Ras mutation
what are colonic adenoma types?
- Tubular = 90% (most common) (>75% tubular)
- Tubulovillous = 10% (less common) (25=50% villous)
- mix between tubular and villous
- Villous ( >50% villous)
- the more villous, the worse it is
what is the anatomy of the adenoma?
- Pedunculated adenomas are on a stalk they look a bit like a tree
- Sessile adenomas are flat and raised
- these can be tubular, tubulovillous or villous
what is the microstructure of tubular adenomas?
- Columnar cells with nuclear enlargement, elongation and multi-layering and loss of polarity. - Proliferation. - Reduced differentiation. - Complexity/disorganisation of architecture.
what is the microstructure of villous adenomas?
- Mucinous cells with nuclear enlargement, elongation, multi-layering, and loss of polarity
-
Exophytic -frond-like extension
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what is dysplasia?
abnormal growth of cells with same features of cancer - categorised into indefinite, low grade and high grade
what is FAP?
- this stands for Familial Adenomatous Polyposis
- it is a 5q21 gene mutation
- the site of mutation determines clinical variants
- i.e. classic, attenuated, Gardner, Turcot
- patients with FAP develop thousands and thousands of polyps
what do patients with FAP undergo?
- prophylactic colectomy
how many adults have adenomas at 50?
how many of these adenomas might become cancerous?
- 25% of adults have adenomas at age 50
- 5% become cancers if left
- the adenomas precede carcinomas by 15 years
- Cancers stay at a curable stage for about 2 years.
do larger or smaller polyps have a greater chance of becoming Colonic Adenomas?
larger polyps
what are the genetic pathways in colorectal cancer?
- Adenoma Carcinoma Sequence
- Microsatellite Instability
- Genetic predisposition for colorectal cancer
explain the adenoma-carcinoma sequence?
- if the gene APC is damaged it can lead to colorectal cancer
- what are microsites?
- what is microsatellite instability?
- Microsatellites are repeat sequences that are prone to misalignment
- some microsatellites are in coding sequences of genes which inhibit growth or apoptosis
what is mismatch repair genes?
what is HNPCC?
- Mis match repair genes recessive genes requiring two hits = without this, there is a very elevated risk of cancer
- HNPCC is when there is a
what are the main genetic pathways leading to colorectal cancer?
- FAP – inactivation of APC TSG.
HNPCC – microsatellite instability
why is APC so important in colon cancer?
in which countries is colorectal cancer common?
which countries is colorectal cancer not common?
- High in USA, Eastern Europe and Australia
- Low in Japan, Mexico and Africa
which dietary factors pre dispose to colorectal cancer?
- high fat
- low fibre
- high red meat
- refined carbohydrates.
these are all food which increase the likelihood of colorectal cancer
how does high temperature affect foods?
High temperature cooking can modify chemicals further in food and induce mutagenic chemicals.
which food deficiencies might lead to colorectal cancer?
- a deficiency in folate and MTHFR
why does a deficiency of folate increase chance of colorectal cancer?
- Folates are important co=enzymes for nucleotide synthesis and DNA
methylation
why does a deficiency in MTHFR increase risk of colorectal cancer?
- Deficiency leads to disruption in DNA synthesis causing DNA instability and this leads to mutation
- Decreased methionine synthesis leads to genomic hypomethylation and focal hypermethylation (this can have gene activating and gene silencing effects)
which foods have anti carcinogenic elements?
- Vitamin C and E
- ROS scavengers.
- Polyphenols
- – green tea and fruit juice.
- Isothiocyanates
- – cruciferous vegetables
what is the clinical presentation of colorectal cancer?
- Change in bowel habit. - Pre-rectal bleeding - Unexplained iron deficient anaemia - mucus pre-rectal production - bloating - cramps - weight loss and fatigue.
what are the macroscopic features of colorectal cancer?
- Small carcinomas may be present within larger polypoid adenomas
what is the distribution of where carcinomas appear within the colon?
- Caecum/Ascending Colon = 22%
- Transverse Colon = 11%
- Descending Colon = 6%
- RECTOSIGMOID = 55%
what are the microscopic features of carcinomas?
- Almost all are adenocarcinomas.
- Mucinous carcinoma (type of
- Signet ring cell carcinoma.
- Neuroendocrine carcinoma (rare).
how can colorectal cancer be graded?
- we can grade CRC by the proportion of gland differentiation
- we use dukes classification
10% are well differentiated\
70% are moderately differentiated
what are the stages of Dukes classification?
- Dukes A
Growth limited to the wall (muscularis propria)
Nodes negative
- Dukes B
Growth beyond muscularis propria
Nodes negative
- Dukes C1
Nodes are positive
Apical lymph node negative
- Dukes C2
what clinical features affect prognosis?
- Diagnosis of asymptomatic patients
- Rectal bleeding as presenting symptom (improves prognosis) o Bowel obstruction (diminished prognosis)
- Tumour location
- Age < 30 (diminished prognosis)
- Preoperative serum CEA (carcinoembryonic antigen) (diminished prognosis with high CEA)
- Distant metastases (markedly diminished prognosis)
which pathological features affect the prognosis of colorectal cancer?
- Depth of bowel wall penetration (increased penetration = diminished
- prognosis)
- Number of regional lymph nodes involved
- Degree of differentiation
- Mucinous (colloid) or signet ring cell (diminished prognosis) o Lymphatic invasion (diminished prognosis)
- Venous invasion (diminished prognosis)
- Perineural invasion (diminished prognosis)
- Local inflammation and immunologic reaction (improved prognosis)
what are the criteria for screening for colorectal cancer?
- Previous adenoma
- 1st degree relative affected by colorectal cancer before the age of 45
- 2 affected first degree relatives
- Evidence of dominant familial cancer trait including colorectal, uterine, and other cancers
- Ulcerative colitis and Crohn’s disease
- Hereditable cancer families (include other sites)
what does the NHS screening for colon cancer consist of?
- They look for Faecal Occult Blood (FOB)
- From 55 years onwards they will send a FOB test kit
- if there is blood present an endoscopy is performed
55-60 = sigmoidoscopy
>60 = full colonoscopy
