Colorectal Cancer Flashcards
Two categories of colorectal neoplasia?
Benign (adenoma)
Malignant (adenocarcinoma)
Types of colorectal polyps?
Inflammatory, e.g: in IBD
Hamartomatous are juvenile polyps
Metaplastic (change in mature mucosal type)
Neoplastic (ADENOMAS)
2 types of neoplastic polyps (adenomas) and which is assoc. with an increased malignancy risk?
Tubular - formation of glands and tubules
Villous - formation of villi (increased risk of malignancy)
Explain the steps in the adenoma-carcinoma sequence
- Small adenoma forms when there is the 1st mutation, usually in the APC gene (adenomatous polyposis coli)
- Large adenoma forms when other mutations occur, e.g: commonly in the Kras gene
- Mutations occur in p53 and other important genes; also, there can be chromosomal deletions
Which chromosomal deletion is assoc. with invasive cancer?
18q loss
4 gene types assoc. with cancer and their role?
Oncogenes - promote cell growth and division but, when mutated, cause excess growth and division
Tumour suppressor genes - suppress growth and division but, when mutated, allow cell growth and division
Macroscopic appearance of colorectal cancer?
Polypoidal - tumor arranged as finger-like processes or as a solid spherical nodule projecting from an epithelial surface
Ulcerative -
Annular - grow centripetally (ring-like) forming what radiologists call an apple core lesion, that constricts the colon
In which regions does colorectal carcinoma tend to occur?
Rectum, distal sigmoid colon and then caecum
3 types of adenocarcinoma, in relation to differentiation, and that these phrases mean?
Well differentiated - there are still normal features of the tissue, e.g: mucin producing
Moderately differentiated
Poorly differentiated - can no longer determine original tissue
Two staging methods of colorectal cancer?
Dukes’ - A, B, C and D
TNM (Tumour, Node, Metastases)
What do Dukes A, B, C and D mean?
A - limited to muscularis mucosae
B - extension through muscularis mucosae
C - involvement of regional lymph nodes
D - distant metastases
Explain the TNM staging?
T1 - submucosa only
T2 - into muscle
T3 - through muscle
T4 - adjacent structures (including peritoneum)
N0 - no lymph node involvement
N1 - 3 nodes involved
M0 - no distant metastases
M1 – distant metastases
What does local spread mean?
To adjacent structures
What does lymphatic spread of colorectal cancer mean?
To pericolic nodes and/or perivascular nodes
What does blood spread of colorectal cancer mean?
Usually, to liver and lungs
What does transcoelomic spread of colorectal cancer mean?
Peritoneal cavity
3 factors contributing to colorectal cancer development?
Environment, genetic factors and predisposing conditions
Protective factors against development of colorectal cancer?
Vegetable, fibre and EXERCISE
Causative factors against development of colorectal cancer?
Red and processed meat, smoking, alcohol and OBESITY
Describe the role of AMP kinase (AMPK) in colorectal cancer development
LKB1 (a tumour suppressor) activates AMPK, which increases glucose uptake my muscle cells and decreases cell turnover
How does exercise affect AMPK?
Exercise increases the activity of AMPK and so there is less cell turnover (and increased glucose uptake by muscle cells)
Two types of autosomal dominant inheritance of colorectal cancer?
FAP (Familial Adenomatous Polyposis)
HNPCC (Hereditary Non-Polyposis Colorectal carcinoma)
Describe FAP
Germ-line mutation in APC gene that dramatically increases colorectal cancer risk
Describe HNPCC
Mutation in DNA mis-match repair gene that also increases risk of colorectal cancer
