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Yr 2 - EMS > Behaviour of Tumours > Flashcards

Behaviour of Tumours Flashcards

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
Q

How does metastasis occur via lymphatics?

A

Form secondary tumours in lymph nodes

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26
Q

What is the lymphatic route most common initially for?

A

Carcinomas

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27
Q

What is the haematogenous route most common for?

28
Q

What organs are most commonly involved in the haematogenous route of metastasis?

A

Liver, lung, bone and brain

29
Q

Where do bone metastases most commonly come from?

A
  • Lung
  • Breast
  • Kidney
  • Thyroid
  • Prostate
30
Q

What is transcoelomic metastasis?

A

Spread across the peritoneal or pleural cavity –> will lead to an effusion containing neoplastic cells

E.g. ovarian cancer

31
Q

What is implantation metastasis?

A

E.g. spilling of tumour cells during surgery

32
Q

What is angiogenesis?

A

Growth of blood vessels on existing vascularture

33
Q

How does angiogenesis play a key role in cancer?

A

Tumours are unable to grow larger than 2-3mm without angiogenesis

34
Q

What do tumour cells express to promote angiogenesis?

A

Vascular endothelial growth factor (VEGF)

35
Q

How is a normal balance kept in angiogenesis?

A
  • Inhibitors:
    • Endostatin
    • TIMP
  • Promoters:
    • VEGF/VEGFR
    • MMP
36
Q

What is point of staging and grading cancer?

A
  • Prognosis
  • Treatment
  • Research
37
Q

What does a cancer stage refer to?

A

The extend of tumour spread:

  • Has the tumour metastasised?
  • Histopathological examination of specimen
  • Radiology
38
Q

What does a cancer ‘grade’ refer to?

A

How aggressive is the tumour? (i.e. how quick will it grow)

  • How different does it look from the tissue of origin?
39
Q

Grade and stage diagram

40
Q

What system is typically used to stage tumours?

A

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
Q

Breast TNM staging:

42
Q

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
A

TNM stage: T3, N1, Mx

43
Q

Breast cancer fiver-year net survival by stage

44
Q

What is Duke’s staging system?

A

The Dukes staging system is a classification system for colorectal cancer

45
Q

Describe A of Dukes Staging System

A

Invades into but not through the bowel wall

46
Q

Describe B of Dukes Staging System

A

Invades through the bowel wall, but no LN metastases

47
Q

Describe C of Dukes Staging System

A

Local lymph nodes involved

48
Q

Describe D of Dukes Staging System

A

Distant metastases

49
Q

How is lymphoma staged?

A
  • 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
Q

What things are considered when grading a tumour?

A
  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
Q

What is differentiation divided into?

A
  • Well differentiated
    • Closely resemble those of normal tissue –> low grade
  • Moderately differentiated
  • Poorly differentiated
    • Cells hardly resemble those of normal tissue –> high grade
52
Q

Well vs poorly differentiated bowel cancer

53
Q

What is pleomorphism?

A

Variation of cells and nuclei in size & shape

54
Q

What are mitoses an indication of?

A
  • Proliferation –> Mitoses are coupled to cell proliferation
  • High grade tumour –> lots of mitoses
55
Q

Mitoses can be seen in normal tissue and do not always indicate malignancy. What type of mitotic figures are seen in malignancy?

A

Atypical and bizzare:

  • Tripolar
  • Quadripolar
  • Multipolar spindles
56
Q

What are mitotic figures?

A

the spindle-shaped figure presented (as by the chromosomes, asters) during mitosis.

57
Q

Grade vs outcome

58
Q

Which of these is not a hallmark of malignancy:

a) invasion
b) mitoses
c) angiogenesis
d) metastasis

A

c) mitoses

59
Q

How do carcinomas usually metastasise?

A

Through the lymphatics

60
Q

What is the most commonly used staging system for malignancy?

61
Q

What is the Ann-Arbor staging system?

A

The landmark lymphoma staging classification

62
Q

What is Gleason staging?

A

Gleason score for grading prostate cancer

63
Q

‘Variation in size and shape of cells’ - what term does this relate to?

A

Pleomorphism

64
Q

When we look at how much the tumour cells look like the normal cells of that tissue, what are we judging?

A

Differentiation

65
Q

What are these?

A

Mitotic figures

Yr 2 - EMS (60 decks)

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