Behaviour of tumours

Question 1

What is the difference between invasion and metastasis?

Answer 1

Invasion if of local tissues and destroys normal tissue, at this point the cancer is still a local disease
Metastasis is the spreading from the site of origin to distant sites and forming new tumours in these areas
At this point the cancer has become a systemic disease

Question 2

How many cancer patients are killed by metastatic disease?

Answer 2

Half

Question 3

What proportion of breast cancer patients are killed by metastatic disease?

Answer 3

1/3

Question 4

What proportion of lung cancer patients are killed by metastatic disease?

Answer 4

Majority

Question 5

What proportion of patients with basal cell carcinoma are killed by metastatic disease?

Answer 5

Essentially none

Question 6

By what basic mechanisms do tumour cells start to invade local tissues?

Answer 6

1) Increased motility
2) Decreased adhesion
3) Mechanical pressure
4) Production of proteolytic enzymes

Question 7

What are the 2 classes of adhesion molecule which are lost in malignant cells?

Answer 7

Cell to cell adhesion molecules - cadherins

Cell to matrix adhesion molecules - integrins

Question 8

What changes occur leading to a reduction in adhesion of malignant cells?

Answer 8

Mutation of E-cadherin in malignant cells leads to loss of cell-cell adhesion and contact inhibition
Changes in integrin expression in malignant cells lead to decreased cell-matrix adhesion

Question 9

What is meant by the epithelial-mesenchymal transition?

Answer 9

Occurs in malignancy epithelial cells gain mesenchymal properties and can invade and migrate. Eg. epithelial cells are tightly connected polarised and tethered whereas mesenchymal cells are loosely connected and able to migrate

Question 10

What is the role or proteolytic enzymes in invasion?

Answer 10

They are matrix metalloproteinases produced by the malignant cells which degrade the extracellular matrix

Question 11

Interstitial collagenases are produced by malignant cells, what do they degrade?

Answer 11

Collagen types I, II, III

Question 12

Gelatinases are produced by malignant cells, what do they degrade?

Answer 12

Collagen type IV, gelatin

Question 13

Stomolysins are produced by malignant cells, what do they degrade?

Answer 13

Collagen type IV, proteoglycans

Question 14

What is the main constituent of extracellular space?

Answer 14

Collagen

Question 15

Are metalloproteinases produced by healthy cells?

Answer 15

Yes, they play a role in normal tissue regulation and are balanced by tissue inhibitors of metalloproteinases

Question 16

How does the balance between metalloproteinases and inhibitors change in malignancy?

Answer 16

Increase in metalloproteinases and decrease in tissue inhibitors of metalloproteinases so they are no longer balanced, this favours tissue breakdown

Question 17

What is the role of metalloproteinases in normal tissue regulation?

Answer 17

Needed to mop up collagen and remodel tissues etc.

Question 18

How does mechanical pressure contribute to invasion?

Answer 18

Uncontrolled proliferation forms a mass
Pressure occludes vessels
Get pressure atrophy
Tumour spreads along the line of least resistance

Question 19

Name the 4 routes of metastasis?

Answer 19

1) Lymphatic
2) Blood
3) Transcoloemic
4) Implantation - spillage of tumour during biopsy/surgery etc.

Question 20

Give 4 cancers which commonly metastasize by the blood route?

Answer 20

1) Liver
2) Lungs
3) Bone
4) Brain

Question 21

What is meant by the transcoloemic route of metastasis?

Answer 21

Across peritoneal, pleural, pericardial cavities or in CSF

Question 22

Name the 5 stages of metastasis?

Answer 22

1) Detachment invasion
2) Intravasation (invasion of cancer cells through the basement membrane into blood vessels or lymphatics)
3) Survival against host defences
4) Adherence extravasation (from the lymph or blood vessels into surrounding tissues)
5) Growth (involving angiogenesis)

Question 23

Carcinomas commonly spread by which route?

Answer 23

Lymphatic

Question 24

Sarcomas commonly spread by which route?

Answer 24

Blood

Question 25

Bone metastases are common in what 5 cancers?

Answer 25

1) Breast 2) Prostate 3) Lung 4) Kidney 5) Thyroid

Question 26

Ovarian cancer commonly spreads by which route?

Answer 26

Transcoloemic

Question 27

Brain and adrenal metastases commonly come from which cancer?

Answer 27

lung cancer

Question 28

What 2 types of bone metastases can occur?

Answer 28

Bone metastases can by: Lytic (lung) Sclerotic (prostate)

Question 29

What are the 2 different theories about patterns of metastasis?

Answer 29

1) Mechanical hypothesis - pattern in dictated by anatomy eg. lymphatic drainage 2) Seed and soil hypothesis - malignant cells can travel anywhere, but 'seeds' are more likely to grow on good soil - ie organs with a good tissue environment for malignant cells

Question 30

Why can people recover from a cancer and then present years later with metastases?

Answer 30

Metastatic cells can remain dormant for years

Question 31

How is organ selectivity for metastasis explained?

Answer 31

Tissue environment is important in the development of metastases

Question 32

What role does angiogenesis have in metastasis?

Answer 32

Essential if metastases are to grow larger than 1-2 mm

Question 33

Factors promoting angiogenesis are produced by what 3 types of cells?

Answer 33

Tumour cells, stromal cells and inflammatory cells

Question 34

Name 3 factors which promote angiogenesis?

Answer 34

VEGF PDGF TGF-beta

Question 35

Name 4 inhibitors of angiogenesis?

Answer 35

ECM proteins Thrombospondin Canstatin Endostatin

Question 36

How does the balance between promotors and inhibitors of angiogenesis change in metastasis and why?

Answer 36

Promotor expression increases and outnumber inhibitor expression, not only are promotors produced by tumour cells, the tumour cells illicit an inflammatory response which leads to the stromal and inflammatory cells produced these promotors which further contributes to the formation of new blood vessels

Question 37

Give 3 reasons to stage and grade a tumour?

Answer 37

1) Determine prognosis - survival time, quality of life 2) Decide how to treat a tumour 3) Research - compare therapies or prognostic factors

Question 38

What is meant by stage of a tumour?

Answer 38

How advanced the tumour is. Has the cancer spread and if so what is the extent of the spread. If you had an arrow depicting cancer disease course from pre-invasive to death stage would tell you how far along the arrow the tumour is

Question 39

What is meant by the grade of a tumour?

Answer 39

How aggressive is the tumour and how different does it look from the tissue of origin If you had an arrow depicting cancer disease course from pre-invasive to death grade would tell you how fast the tumour is moving along the arrow

Question 40

Tumours are staged using TMN what does this stand for?

Answer 40

T=tumour M=metastases N=nodes Each organ has an individual TMN system, stage can be clinical, pathological or radiological

Question 41

How does TMN staging basically work?

Answer 41

T = size and extend of primary tumour M = presence and extent of distant metastases N = presence and number of lymph node metastases TMN can be combined to give and overall stage for the tumour from 1-4

Question 42

How does the stage of a breast cancer affect the treatment?

Answer 42

1 - surgery only 2 - surgery and radiotherapy 3 - surgery and chemo 4 - chemo

Question 43

What is Duke's staging for colorectal cancer?

Answer 43

``` A = invades into, but not through bowel wall B = invades through the bowel wall but with no lymph node metastases C = local lymph nodes involved D = distant metastases ```

Question 44

How does Duke's staging for colorectal cancer correlate with survival?

Answer 44

``` A = >90% 5 year survival B = 70% 5 year survival C = 30% 5 year survival D = 5-10% 5 year survival ```

Question 45

Grading is performed by which specialists?

Answer 45

Histopathologists

Question 46

What is grading based on?

Answer 46

Differentiation - how much does the tumour resemble the tissue it originates from Nuclear pleomorphism and size Mitotic activity Necrosis

Question 47

How do grade and stage correlate with outcome?

Answer 47

Both correlate well with outcome

Question 48

What 3 things lead to systemic malignant disease?

Answer 48

1) Invasion 2) Metastasis 3) Angiogenesis