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Y2 MECHANISMS OF DISEASE > Behaviour of Tumours > Flashcards

Behaviour of Tumours Flashcards

1
Q

What is the definition of neoplasia?

A

the presence or formation of new, abnormal growth of tissue

this involves loss of normal growth control

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2
Q

What is the difference between benign and malignant?

A

benign:

  • no local invasion
  • no metastasis

malignant:

  • local invasion and metastasis
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3
Q

What is the difference between hypertrophy and hyperplasia?

A

hypertrophy:

enlargement in size of individual cells

hyperplasia:

increase in number of cells

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4
Q

How are metaplasia, dysplasia and anaplasia involved in cancer?

A

metaplasia is replacement of mature tissue types

dysplasia is abnormality indicating precursor change of malignancy

anaplasia involves the failure to differentiate - this is malignancy

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5
Q

What is the difference between metaplasia, dysplasia and anaplasia?

A

metaplasia:

abnormal change in the nature of a tissue

dysplasia:

abnormal development of cells

anaplasia:

cells have poor cellular differentiation and lose the morphological characterstics of mature cells

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6
Q

How does cancer go from being a local disease to a syatemic disease?

A

local disease - invasion:

  • invades adjacent normal tissue
  • destroys normal tissue

systemic disease - metastasis:

  • spreads from site of origin to distant sites and forms new tumours in these areas
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7
Q

Which types of patients and cancers usually present with metastatic disease?

A

half of all adult cancer patients and the majority of paediatric patients at presentation

the majority of lung cancer patients and 1/3 of breast cancer patients

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8
Q

Which type of cancer patients are hardly ever affected by metastatic disease?

A

essentially all patients with basal cell carcinoma

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9
Q

What are the characteristics of cancer cells during invasion?

What can encourage invasion?

A
  1. increased motility
  2. decreased adhesion
  3. production of proteolytic enzymes

mechanical pressure encourages invasion

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10
Q

What types of molecules are represented by the blue and red lines?

A

blue - cadherins

  • these are cell to cell adhesion molecules

red - integrins

  • these are cell to matrix adhesion molecules
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11
Q

How can changes in cadherins and integrins influence invasion by cancer cells?

A

cadherins:

  • mutation of E-cadherin leads to loss of cell-cell adhesion and contact inhibition

integrins:

  • changes in integrin expression lead to decreased cell-matrix adhesion

These changes lead to less adhesion and more motility

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12
Q

What process, involving epithelial cells, allows cancer to gain less adhesion and more motility, facilitating invasion?

A

Mesenchymal transition

epithelial cells are tightly connected, polarised and tethered

mesenchymal cells are loosely connected and able to migrate

epithelial cells gain mesenchymal properties, allowing them to invade and migrate

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13
Q

What types of proteolytic enzymes are produced in cancer and how do they facilitate invasion?

A

matrix metalloproteinases

they degrade the extracellular matrix, facilitating local invasion

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14
Q

What are the 3 main matrix metalloproteinases produced in cancer and what do they degrade?

A

interstitial collagenases:

  • degrades collagen types I, II and III

gelatinases:

  • degrades collagen type IV and gelatin

stomolysins:

  • degrades collagen type IV and proteoglycans
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15
Q

In terms of presence of metalloproteinases, how does this change in cancer?

A
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16
Q

How does mechanical pressure influence invasion by cancer cells?

A

uncontrolled proliferation forms a mass

pressure occludes vessels and leads to pressure atrophy

the cancer spreads along the lines of least resistance

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17
Q

How does metastasis vary in characteristics from the primary tumour?

A

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

metastasis is often the presenting tumour

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18
Q

When does metastasis tend to occur in cancer development?

A

it occurs at different stages in the natural history of different types of tumour

it can occur early, or more commonly occurs as a late relapse

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19
Q

What are the 4 routes of metastasis and the mechanisms by which they occur?

A

1. lymphatic:

  • cancer spreads to distant or local lymph nodes

2. blood:

  • cancer enters the blood and spreads to liver, lungs, bone, brain, etc.

3. transcoelomic:

  • cancer travels across peritoneal, pleural or pericardial cavities or in the CSF

4. implantation:

  • spillage of tumour during biopsy or surgery
20
Q

What are the following stages involved in metastasis?

A
21
Q

What is meant by “intravasation”?

A

the invasion of cancer cells through the basement membrane into a blood or lymphatic vessel

22
Q

What is meant by “extravasation”?

A

the movement of cancer cells out of a blood vessel and into a tissue during metastasis

23
Q

Where do the following cancers usually spread to first?

  1. carcinomas
  2. sarcomas
A

carcinomas usually spread to lymphatic system

sarcomas usually spread via the blood

24
Q

Which cancers tend to spread first to the bone, brain and adrenal glands and transcoelomic?

A

bone:

  • breast, prostate, lung, kidney, thyroid
  • bone metastases can be lytic (lung) or sclerotic (prostate)

brain and adrenal glands:

  • lung cancer

transcoelomic:

  • ovarian cancer
25
Q

What is meant by the ‘mechanical hypothesis’ to describe the patterns of metastasis?

A

spread is dictated by anatomy

e.g. in GI cancer, there are liver metastases as blood is drained from the gut to the liver

26
Q

What is meant by the ‘seed and soil hypothesis’ to describe patterns of metastasis?

A

when a plant goes to seed, its seeds are carried in all directions, but they can only live and grow if they fall on congenial soil

27
Q

What does the seed and soil hypothesis suggest about the nature of metastases?

A

the tissue environment is important - this influences organ selectivity for metastases

metastatic cells can remain dormant for years

28
Q

What is meant by angiogenesis?

For which types of tumours is this process essential?

A

new blood vessel formation, derived from existing vessels

this is essential if metastases are to grow larger than 1-2mm

29
Q

What are the 3 main promoters of angiogenesis?

Where are they produced?

A

VEGF produced by tumour cells

PDGF produced by stromal cells

TGFß produced by inflammatory cells

30
Q

What are the main inhibitors of angiogenesis?

A

ECM proteins

thrombospondin

canstatin

endostatin

31
Q

What are the main inhibitors and promoters involved in angiogenesis in tumour cells?

A

VEGF is a promoter produced by tumour cells

ECM proteins are inhibitors

32
Q

Why is cancer staged and graded?

A
  1. to determine prognosis - survival time and quality of life
  2. to decide how to treat the tumour
  3. research - to compare therapies or prognostic factors
33
Q

What is the difference between the stage and the grade of a cancer?

A

stage - how advanced is the tumour?

  • has the cancer spread?
  • if so, what is the extent of the spread?

grade - how aggressive is the tumour?

  • how different does the tumour look from its tissue of origin?
34
Q

What are the stages in cancer progression shown?

How can stage and grade be represented on this arrow?

A

stage - how far along the arrow the tumour is

grade - how quickly the tumour progresses along the arrow

35
Q

What is meant by the TMN staging system?

A

T - Tumour

M - Metastases

N - Nodes

each organ has an individual TMN system

stage can be clinical, pathological or radiological

36
Q

How is the TMN staging system used to work out the overall stage for the tumour?

A

T - tumour:

  • size +/- extent of primary tumour

M - metastases:

  • the presence and extent of distant metastases

N - nodes:

  • presence and number of lymph node metastases

TMN is combined to give an overall stage for the tumour from I to IV

37
Q

How is the T stage determined in breast cancer?

A
38
Q

How is the N stage worked out in breast cancer?

A
39
Q

How is the M stage worked out in breast cancer?

A
40
Q

How is breast cancer staging worked out?

A
41
Q

What treatments are offered to patients with breast cancer of different stages?

A

Stage I - surgery only

Stage II - surgery and radiotherapy

Stage III - surgery and chemotherapy

Stage IV - chemotherapy only

42
Q

What are the 4 stages involved in Dukes Staging for colorectal cancer?

A

A - invades into, but not through, the bowel wall

B - invades through the bowel wall but with no lymph node metastases

C - local lymph nodes involved

D - distant metastases

43
Q

What are the 5 year survival percentages associated with each stage in Dukes Staging?

A

A - >90% 5 year survival

B - 70%

C - 30%

D - 5-10%

44
Q

What types of cellular features are looked for when assessing the grade of a cancer?

A
  1. differentiation - how much does the tumour resemble the tissue it originated from?
  2. nuclear pleomorphism and size
  3. mitotic activity
  4. necrosis
45
Q

How is tumour grade usually assessed?

A

tumour grading is subjective as there are a lot of moderate grades

46
Q
A

Y2 MECHANISMS OF DISEASE (36 decks)

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