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EMS - MoD > 22. Behaviour of Tumours > Flashcards

22. Behaviour of Tumours Flashcards

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1
Q

In what ways do tumours behave in local disease?

A

Invasion

  • invades adjacent normal tissue
  • destroys normal tissue
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2
Q

In what way do tumours behave in systemic disease?

A

Metastasis

- spreads from site of origin to distant sites and forms new tumours in these new areas

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3
Q

What is invasion associated with?

A
  • increased motility
  • decreased adhesion
  • production of proteolytic enzymes
  • mechanical pressure
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4
Q

What are the cell to cell adhesion molecules?

A

Cadherins

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5
Q

What are the cell to matrix adhesion molecules?

A

Integrins

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6
Q

What does mutation of E-cadherin lead to?

A

Loss of cell-cell adhesion and contact inhibition

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7
Q

What do changes in integrin expression?

A

Decreased cell-matrix adhesion

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8
Q

What 3 things are involved in less adhesion/more motility?

A
  • cadherins changes
  • integrins changes
  • epithelial-mesenchymal transition
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9
Q

What is the difference between epithelial cells and mesenchymal cells?

A

Epithelial cells - tightly connected, polarised and tethered

Mesenchymal cells - loosely connected, able to migrate

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10
Q

What happens to the epithelial cells in cancer?

A

Epithelial cells gain mesenchymal properties allowing them to invade and migrate

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11
Q

What are matrix metalloproteinases?

A

Enzymes responsible for the degradation of most extracellular matrix proteins

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12
Q

What do interstitial collagenases degrade?

A

Collagen types I, II and III

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13
Q

What degrades collagen type IV and gelatin?

A

Gelatinases

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14
Q

What degrades collagen type IV and proteoglycans?

A

Stomolysins

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15
Q

Name 3 matrix metalloproteinases

A
  • interstitial collagenases
  • gelatinases
  • stomolysins
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16
Q

What do stomolysins degrade?

A

Collage type IV, proteoglycans

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17
Q

What is in balance in normal tissue regulation? (concerning proteolytic enzymes)

A

Matrix metalloproteinases and tissue inhibitors of metalloproteinases are in balance

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18
Q

In cancer, what is out of balance concerning proteolytic enzymes?

A

More matrix metalloproteinases than tissue inhibitors of metalloproteinases - favours ECM breakdown

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19
Q

What causes increased mechanical pressure in cancer?

A

Uncontrolled proliferation forms mass = increased pressure

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20
Q

What is the consequence of increased mechanical pressure in cancer?

A
  • pressure from mass occludes vessels
  • pressure atrophy
  • spread along lines of least resistance
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21
Q

Secondary tumour burden is often what?

A

Secondary tumour burden is often greater than that of the primary site

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22
Q

Give some features of metastasis

A
  • metastasis is often the presenting tumour
  • primary site might be unknown
  • occurs at different stages in natural history in different tumours
  • may be early or more commonly, a late relapse
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23
Q

Give 4 potential metastasis routes

A
  • lymphatic
  • blood
  • transcoelomic
  • implantation
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24
Q

What does the transcoelomic route of metastasis mean?

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A

Across peritoneal, pleural, pericardial cavities or in CSF

25
What does implantation route of metastasis mean?
Spillage of tumour during biopsy/surgery
26
Metastasis by blood occurs in which cancers?
- liver - lungs - bone - brain
27
What are the stages in metastasis?
- detachment - invasion - intravasation - survival against host defences - adherence - extravasation - growth - angiogenesis
28
What is intravasation?
The invasion of cancer cells through the basal membrane into a blood or lymphatic vessel
29
What is extravasation?
Cancer cells exiting the capillaries and entering organs
30
What is the typical pattern of metastasis in carcinomas?
Lymphatic spread first
31
What is the typical pattern of metastasis in sarcomas?
Blood spread first
32
What are the 2 types of bone metastases?
- lytic (bone) | - sclerotic (prostate)
33
What are the 2 hypotheses concerning patterns of metastasis?
- mechanical hypothesis (dictated by anatomy) | - seed and soil hypothesis ("seeds carried in all directions but can only live and grow if they fall on congenial soil")
34
Why is tissue environment important in patterns of metastasis?
Influences organ selectivity for metastases
35
Are metastatic cells always active?
Metastatic cell can remain dormant for years
36
What is angiogenesis?
New vessel formation (derives from existing vessels)
37
What is the role of angiogenesis?
- role in development and healing - role of bone marrow derived endothelial stem cells uncertain - essential if metastases are to grow larger than 1-2mm
38
What are the promoters of angiogenesis?
- VGEF - PDGF - TGFb
39
What are inhibitors of angiogenesis?
- ECM proteins - thrombospondin - canstatin - endostatin
40
Why is staging and grading of cancer important?
- determine prognosis (survival time and quality of life) - decide how to treat the tumour - research (compare therapies or prognostic factors)
41
What is the stage of cancer?
How advanced is the tumour? Has the cancer spread and if so, what is the extent of spread?
42
What is the grade of cancer?
How aggressive is the tumour? How different does it look from tissue of origin?
43
What are stage and grade in terms of the arrow from pre-inavsive to metastasis and death?
Stage = how far along the arrow the tumour is Grade = how quickly the tumour progresses along the arrow
44
Tumours are staged using TMN. What does this stand for?
``` T = tumour M = metastases N = nodes ``` Each organ has an individual TMN system and stage can be clinical, pathological or radiological
45
What is T in TMN staging?
Size and extent of primary tumour
46
What is M in TMN staging?
Presence and extent of distant metastases
47
What is N in TMN staging?
Presence and number of lymph nodes metastases
48
TMN can be combined to give what?
An overall stage for the tumour (I to IV)
49
What are the different T stages in breast cancer staging?
``` Tis = in situ disease T1 = less than 2cm T2 = 2-5cm T3 = over 5cm T4 = involving skin or chest wall ```
50
What are the different N stages in breast cancer staging?
``` N0 = no nodes N1 = ipsilateral nodes N2 = more node involvement ```
51
What are the different M stages in breast cancer staging?
``` M0 = no distant mets M1 = distant mets ```
52
What do the overall stages mean?
``` 0 = Tis I = T1, N0, M0 II = T1/2, N1 or T3 III = T(any), N2 or T4 IV = T(any), N(any), M1 ```
53
How does stage of breast cancer indicate treatment?
Surgery, surgery and radiotherapy, surgery can chemotherapy, just chemotherapy... as stage progresses
54
How does stage correlate with outcome?
Decreased survival at all years with increased stage
55
Describe Dukes staging for colorectal cancer
A = invades into, but not through bowel wall B = invades through bowel wall but with no lymph node metastases C = local lymph nodes involved D = distant metastases
56
How does Dukes staging correlate with survival?
A = over 90% 5yr survival B = 70% 5yr survival C = 30% 5yr survival D = 5-10% 5yr survival
57
What is grading based on?
- differentiation (how much tumour resembles tissue it originates from) - nuclear polymorphism and size - mitotic activity - necrosis
58
Describe basic grading
``` G1 = near normal (well differentiated) G2 = moderately differentiated G3 = poorly differentiated G4 = undifferentiated ```
59
How does marked nuclear atypia affect grade?
Increases grade by one

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