Adenomatous Polyposis Coli - 5q21 gene mutation - Site of mutation determines clinical variants (classic, attenuated, Gardner, Turcot etc) - Many patients have prophylactic colectomy<30

Cancer 13: Cancer as a disease - Colorectal cancer Flashcards by Kieron Young

What parts of the colon can become cancer?

Caecum, ascending, transverse, descending anf sigmoid

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Describe colonic anatomy

See slides

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Describe the turnover of the cells of the colon?

2-5 million cells die per minute in the colon!
Proliferation renders cells vulnerable - the greater the rate of proliferation the greater the chance of a mutation or error.
APC mutation prevents cell loss mutation
Normally we have protective mechanisms to eliminate genetically defective cells by;
1) Natural loss
2) DNA monitors
3) Repair enzymes

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Define polyps?

A polyp is any projection from a mucosal surface into a hollow viscus, and may be hyperplastic, neoplastic, inflammatory, hamartomatous, etc

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Define an adenoma?

An adenoma is a benign neoplasm of the mucosal epithelial cells

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What are the different types of colonic polyps?

Metaplastic/Hyperplastic
Adenomas
Juvenile
Peutz Jeghers
Lipomas 
Others (essentially any circumscribed intramucosal lesions)

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What is a hyperplastic polyp?

See slides

Very common
<0.5 cm
90% of all LI polyps
Often multiple
No malignant potential
15% have k-ras mutation

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What are the different colonic adenoma types?

Tubular (rolls of testtubes) (>75%tubular) 90%
Tubulovillous (25- 50% villous) 10%
Villous (Vila like projections) ( > 50% villous)
(Flat)
(Serrated)

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What is pedunculated and cecile adeomas?

See slides

pedunculated - Tree
Cecile - Lush rug

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Describe the microstructures of tubular adenomas?

Columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
Increased proliferative activity
Reduced differentiation
Complexity/disorganisation of architecture
hyperchromatic nuclei

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Describe the microstructures of villous adenomas?

Mucinous cells with nuclear enlargement, elongation, multilayering and loss of polarity
Exophytic, frond-like extensions
Rarely may have hypersecretory function and result in excess mucus discharge and hypokalemia

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What is dysplasia?

Literal meaning ‘bad growth’. Abnormal growth of cells with some features of cancer

Subjective analysis:
Indefinite, low grade and high grade

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What is APC/FAP?

Adenomatous Polyposis Coli

5q21 gene mutation
Site of mutation determines clinical variants (classic, attenuated, Gardner, Turcot etc)*
Many patients have prophylactic colectomy<30

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Describe colonic adenomas?

25% of adults have adenomas at age 50

5% of these become cancers if left

Large polyps have higher risk than small ones (so 5% > 1 cm 50-60, 15% at 75)

Lead time 10 years - remove the polyp reduces the risk of cancer.

Cancers stay at a curable stage c. 2 years

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Describe the progression from adenoma to carcinoma?

Most CRCs arise from adenomas
Residual adenoma in ~ 10-30% of CRCs
Adenomas and Ca similar distribution
Adenomas usually precede cancer by 15 years
Endoscopic removal of polyps decreases the incidence of subsequent CRC

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Describe the progression from adenoma to carcinoma?

Most CRCs arise from adenomas
Residual adenoma in ~ 10-30% of CRCs
Adenomas and Ca similar distribution
Adenomas usually precede cancer by 15 years
Endoscopic removal of polyps decreases the incidence of subsequent CRC

Many carcinomas are derived from adenomas

What are the 2 genetic predispositions of CRC?

FAP - inactivation of APC tumour suppressor genes

HNPCC - microsatellite instability

Colonic carcinoma

slide 41

Western diet = increased colon cancer

What is the effect food on cancer?

See slide 43 - key is balanced diet without too much high fat food

Has both good and bad stuff

What is the effect of dietary deficiencies on CRC?

slide 46

What is the clinical presentation of CRC?

Changing bowel habit
Bleeding PR (rectal bleeding)
Unexplained Fe deficiency anaemia (more common on the right side)
Mucus
Bloating
Cramps (colic)
Weight loss and fatigue

What is the distribution of CRC?

Caecum/Ascending Colon 22%

Transverse Colon 11%

Descending Colon 6%

Rectosigmoid 55%

What are the different carcinomas that you can get in the large bowel?

Adenocarcinomas Grade 1-3 - Malignant cancer of the glandular epithelium
Mucinous carcinomas
Signet ring cell
Neuroendocrine

What are the different carcinomas that you can get in the large bowel?

Adenocarcinomas Grade 1-3 - Malignant cancer of the glandular epithelium
Mucinous carcinomas
Signet ring cell
Neuroendocrine

Describe the grading of CRC

Proportion of gland differentiation relative to solid areas or nests and cords of cells without lumina ~ 10% well differentiated ~ 70% moderately differentiated ~ 20% poorly differentiated

What is Dukes Classification?

This is used to describe how far the tumour has spread. Dukes was the pioneer of staging - the more its spread the worse you're going to do. Lymph nodes are so important. Dukes A - growth limited to wall - nodes negative Dukes B - growth beyond musc propria - nodes negative Dukes C1 - nodes positive - apical LN negative Dukes C2 - apical LN (all the lymph nodes are in a chain so if the first one is affected then the other ones will most likely be affected to) positive

What clinical features affect prognosis?

See slide 65-66

What are the treatment options for CRC?

Treatment options depend on the stage of the tumour. Surgery/chemo/radio

What is high risk screening for CRC?

High risk screening - 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 - UC and Crohn’s disease - Hereditable cancer families (include other sites)

What is population screening for colon caner?

Screening is the practice of investigating apparently healthy individuals with the object of detecting unrecognised disease or people with an exceptionally high risk of developing disease, and of intervening in ways that will prevent the occurrence of disease or improve the prognosis when it develops. Use of feacal occult blood