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Yr 2 - EMS > Behaviour of Tumours > Flashcards

Behaviour of Tumours Flashcards

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1
Q

What is invasion of tumours?

A

Tumour invades adjacent normal tissue and starts to destroy it

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2
Q

What is metastasis of tumours?

A

Spreads from site of origin to a distant site and establishes a new tumour there

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3
Q

What causes the progression from local disease to systemic disease?

A

Invasion –> metastasis

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4
Q

How are epithelial cells normally connected?

A

Tightly connected, polarised and tethered to each other (unable to move)

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5
Q

How are mesenchymal cells normally connected?

A

Loosely connected, able to migrate

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6
Q

What is the epithelial-mesenchymal transition?

A

In cancer, epithelial cells gain MESENCHYMAL properties and can invade and migrate

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7
Q

How do epithelial cells gain mesenchymal properties?

A
  1. Increased motility
  2. Decreased adhesion
  3. Production of proteolytic enzymes
  4. Mechanical pressure
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8
Q

What is an example of a cell-to-cell adhesion molecule (CAM)?

A

Cadherins: important in the formation of adherens junctions to bind cells with each other.

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9
Q

What can a mutation in E-cadherin in the tumour lead to?

A

reduced cell to cell adhesion

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10
Q

What is an example of a cell to matrix adhesion molecule and receptor?

A

Integrin: the principal receptors used by animal cells to bind to the extracellular matrix.

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11
Q

What can changes in integrin expression (as seen in tumours) lead to?

A

Decreased cell-matrix adhesion

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12
Q

What is the most important proteolytic enzyme in neoplastic invasion?

A

Matrix metalloproteinases

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13
Q

What are matrix metalloproteinases secreted by?

A

Malignant neoplastic cells

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14
Q

What are matrix metalloproteinases able to digest ?

A

Able to digest surrounding connective tissue

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15
Q

What are the 3 major types of matrix metalloproteinases?

A
  1. Interstitial collagenases
  2. Gelatinases
  3. Stromelysins
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16
Q

What do interstitial collagenases degrade?

A

Type I, II and III collagen

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17
Q

What do gelatinases degrade?

A

Type IV collagen and gelatin

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18
Q

What do stromelysins degrade?

A

Type IV collagen and proteoglycans

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19
Q

The balance of proteolytic enzymes in normal vs cancer?

A
  • Normal: balance between tissue inhibitors of metalloproteinases and matrix metalloproteinases
  • Cancer: more matrix metalloproteinases so cancer favours extracellular matrix breakdown
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20
Q

Uncontrolled proliferation and invasion can lead to a mass. How can a mass affect vessels?

A

Mass can occlude vessels or put pressure on tissues –> clinical effects on patients

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21
Q

Malignant neoplasms invade along the ‘path of least resistance’. What does this mean?

A
  • Most commonly along blood vessels or nerves
  • Cartilage and bone are extremely resistant to neoplastic invasion
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22
Q

Describe the tumour mass of a secondary tumour (metastasis) compared to the primary tumour

A

Often tumour mass of secondary tumours exceeds that of the primary lesion. May be presenting clinical feature:

  • Bone lesions
  • Palpable lymph nodes
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23
Q

Metastatic sequence:

A
  • Detachment and invasion (cancer cells detach from primary tumour)
    • loss of surface adhesion molecules and imbalance of matrix metalloproteinases
      • ECM is broken down
      • Neoplastic cells are motile
  • Intravasation
    • The invasion of cancer cells through the basement membrane
  • Survival against host defences
    • Often have a reduced expression of the MHC complex on their surfaces
  • Adherence and extravasation
    • Adhere to lining of blood vessel at the distant site
    • Movement of cells out of a blood vessel into tissue during metastasis
  • Angiogenesis
    • Ability to promote formation of new blood vessels
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24
Q

What are the 4 main routes of metastasis?

A
  1. Lymphatics
  2. Haematogenous (blood)
  3. Transcoelomic
  4. Implantation
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25
How does metastasis occur via lymphatics?
Form secondary tumours in lymph nodes
26
What is the lymphatic route most common initially for?
Carcinomas
27
What is the haematogenous route most common for?
Sarcomas
28
What organs are most commonly involved in the haematogenous route of metastasis?
Liver, lung, bone and brain
29
Where do bone metastases most commonly come from?
* Lung * Breast * Kidney * Thyroid * Prostate
30
What is transcoelomic metastasis?
Spread across the peritoneal or pleural cavity --\> will lead to an effusion containing neoplastic cells E.g. ovarian cancer
31
What is implantation metastasis?
E.g. spilling of tumour cells during surgery
32
What is angiogenesis?
Growth of blood vessels on existing vascularture
33
How does angiogenesis play a key role in cancer?
Tumours are unable to grow larger than 2-3mm without angiogenesis
34
What do tumour cells express to promote angiogenesis?
Vascular endothelial growth factor (VEGF)
35
How is a normal balance kept in angiogenesis?
* Inhibitors: * Endostatin * TIMP * Promoters: * VEGF/VEGFR * MMP
36
What is point of staging and grading cancer?
* Prognosis * Treatment * Research
37
What does a cancer stage refer to?
The extend of tumour ***spread***: * Has the tumour metastasised? * Histopathological examination of specimen * Radiology
38
What does a cancer 'grade' refer to?
How aggressive is the tumour? (i.e. how quick will it grow) * How different does it look from the tissue of origin?
39
Grade and stage diagram
40
What system is typically used to stage tumours?
TNM: based on the anatomical extend of spread * T - extent of tumour spread * T0: no evidence of primary tumour * T1-4: increasing size/invasion of tumour * N - extent of nodal spread * N0: no regional node metastases * N1-3: increasing involvement of nodes * M - presence or absence of distant metastases * M0: no distant metastases * M1: distant metastases present
41
Breast TNM staging:
42
Using the breast TNM staging, what is the TNM stage for this tumour: * Measures 3cmx6cmx3cm * Does not involve chest wall * 13 nodes examined (same side as lesion) * 4 nodes were positive for metastases * Unable to comment on distant metastatic disease
TNM stage: T3, N1, Mx
43
Breast cancer fiver-year net survival by stage
44
What is Duke's staging system?
The Dukes staging system is a classification system for colorectal cancer
45
Describe A of Dukes Staging System
Invades into but not through the bowel wall
46
Describe B of Dukes Staging System
Invades through the bowel wall, but no LN metastases
47
Describe C of Dukes Staging System
Local lymph nodes involved
48
Describe D of Dukes Staging System
Distant metastases
49
How is lymphoma staged?
* Stage I * Lymphoma in ***one group*** of lymph nodes * Stage II * Lymphoma in ***2 or more groups*** of lymph nodes * Stage III * Lymphoma ***both sides of diaphragm*** * Stage IV * Lymphoma in organ not part of lymphatics / lymphoma in bone marrow, liver or lung Further classified depending on presence or absence of systemic symptoms (e.g. weight loss, fever etc) * A - symptoms absent * B - symptoms present
50
What things are considered when grading a tumour?
1. How much do the cancer cells resemble the normal tissue; ***differentiation*** 2. The variation in size and shape of the cancer cells; ***pleomorphism*** 3. How many cells are actively dividing, can count mitotic figures; ***proliferation***
51
What is differentiation divided into?
* Well differentiated * Closely resemble those of normal tissue --\> **low grade** * Moderately differentiated * Poorly differentiated * Cells hardly resemble those of normal tissue --\> **high grade**
52
Well vs poorly differentiated bowel cancer
53
What is pleomorphism?
Variation of cells and nuclei in ***size & shape***
54
What are mitoses an indication of?
* Proliferation --\> Mitoses are coupled to cell proliferation * High grade tumour --\> lots of mitoses
55
Mitoses can be seen in normal tissue and do not always indicate malignancy. What type of mitotic figures are seen in malignancy?
Atypical and bizzare: * Tripolar * Quadripolar * Multipolar spindles
56
What are mitotic figures?
the spindle-shaped figure presented (as by the chromosomes, asters) during mitosis.
57
Grade vs outcome
58
Which of these is not a hallmark of malignancy: a) invasion b) mitoses c) angiogenesis d) metastasis
c) mitoses
59
How do carcinomas usually metastasise?
Through the lymphatics
60
What is the most commonly used staging system for malignancy?
TNM
61
What is the Ann-Arbor staging system?
The landmark lymphoma staging classification
62
What is Gleason staging?
Gleason score for grading prostate cancer
63
'Variation in size and shape of cells' - what term does this relate to?
Pleomorphism
64
When we look at how much the tumour cells look like the normal cells of that tissue, what are we judging?
Differentiation
65
What are these?
Mitotic figures

Yr 2 - EMS (60 decks)

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