Behaviour of Tumours Flashcards
What is the definition of neoplasia?
the presence or formation of new, abnormal growth of tissue
this involves loss of normal growth control
What is the difference between benign and malignant?
benign:
- no local invasion
- no metastasis
malignant:
- local invasion and metastasis
What is the difference between hypertrophy and hyperplasia?
hypertrophy:
enlargement in size of individual cells
hyperplasia:
increase in number of cells
How are metaplasia, dysplasia and anaplasia involved in cancer?
metaplasia is replacement of mature tissue types
dysplasia is abnormality indicating precursor change of malignancy
anaplasia involves the failure to differentiate - this is malignancy
What is the difference between metaplasia, dysplasia and anaplasia?
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
How does cancer go from being a local disease to a syatemic disease?
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
Which types of patients and cancers usually present with metastatic disease?
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
Which type of cancer patients are hardly ever affected by metastatic disease?
essentially all patients with basal cell carcinoma
What are the characteristics of cancer cells during invasion?
What can encourage invasion?
- increased motility
- decreased adhesion
- production of proteolytic enzymes
mechanical pressure encourages invasion
What types of molecules are represented by the blue and red lines?
blue - cadherins
- these are cell to cell adhesion molecules
red - integrins
- these are cell to matrix adhesion molecules
How can changes in cadherins and integrins influence invasion by cancer cells?
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
What process, involving epithelial cells, allows cancer to gain less adhesion and more motility, facilitating invasion?
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
What types of proteolytic enzymes are produced in cancer and how do they facilitate invasion?
matrix metalloproteinases
they degrade the extracellular matrix, facilitating local invasion
What are the 3 main matrix metalloproteinases produced in cancer and what do they degrade?
interstitial collagenases:
- degrades collagen types I, II and III
gelatinases:
- degrades collagen type IV and gelatin
stomolysins:
- degrades collagen type IV and proteoglycans
In terms of presence of metalloproteinases, how does this change in cancer?
How does mechanical pressure influence invasion by cancer cells?
uncontrolled proliferation forms a mass
pressure occludes vessels and leads to pressure atrophy
the cancer spreads along the lines of least resistance
How does metastasis vary in characteristics from the primary tumour?
the secondary tumour burden is often greater than that of the primary site
metastasis is often the presenting tumour
When does metastasis tend to occur in cancer development?
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
What are the 4 routes of metastasis and the mechanisms by which they occur?
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
What are the following stages involved in metastasis?
What is meant by “intravasation”?
the invasion of cancer cells through the basement membrane into a blood or lymphatic vessel
What is meant by “extravasation”?
the movement of cancer cells out of a blood vessel and into a tissue during metastasis
Where do the following cancers usually spread to first?
- carcinomas
- sarcomas
carcinomas usually spread to lymphatic system
sarcomas usually spread via the blood
Which cancers tend to spread first to the bone, brain and adrenal glands and transcoelomic?
bone:
- breast, prostate, lung, kidney, thyroid
- bone metastases can be lytic (lung) or sclerotic (prostate)
brain and adrenal glands:
- lung cancer
transcoelomic:
- ovarian cancer
What is meant by the ‘mechanical hypothesis’ to describe the patterns of metastasis?
spread is dictated by anatomy
e.g. in GI cancer, there are liver metastases as blood is drained from the gut to the liver
What is meant by the ‘seed and soil hypothesis’ to describe patterns of metastasis?
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
What does the seed and soil hypothesis suggest about the nature of metastases?
the tissue environment is important - this influences organ selectivity for metastases
metastatic cells can remain dormant for years
What is meant by angiogenesis?
For which types of tumours is this process essential?
new blood vessel formation, derived from existing vessels
this is essential if metastases are to grow larger than 1-2mm
What are the 3 main promoters of angiogenesis?
Where are they produced?
VEGF produced by tumour cells
PDGF produced by stromal cells
TGFß produced by inflammatory cells
What are the main inhibitors of angiogenesis?
ECM proteins
thrombospondin
canstatin
endostatin
What are the main inhibitors and promoters involved in angiogenesis in tumour cells?
VEGF is a promoter produced by tumour cells
ECM proteins are inhibitors
Why is cancer staged and graded?
- to determine prognosis - survival time and quality of life
- to decide how to treat the tumour
- research - to compare therapies or prognostic factors
What is the difference between the stage and the grade of a cancer?
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?
What are the stages in cancer progression shown?
How can stage and grade be represented on this arrow?
stage - how far along the arrow the tumour is
grade - how quickly the tumour progresses along the arrow
What is meant by the TMN staging system?
T - Tumour
M - Metastases
N - Nodes
each organ has an individual TMN system
stage can be clinical, pathological or radiological
How is the TMN staging system used to work out the overall stage for the tumour?
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
How is the T stage determined in breast cancer?
How is the N stage worked out in breast cancer?
How is the M stage worked out in breast cancer?
How is breast cancer staging worked out?
What treatments are offered to patients with breast cancer of different stages?
Stage I - surgery only
Stage II - surgery and radiotherapy
Stage III - surgery and chemotherapy
Stage IV - chemotherapy only
What are the 4 stages involved in Dukes Staging for colorectal cancer?
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
What are the 5 year survival percentages associated with each stage in Dukes Staging?
A - >90% 5 year survival
B - 70%
C - 30%
D - 5-10%
What types of cellular features are looked for when assessing the grade of a cancer?
- differentiation - how much does the tumour resemble the tissue it originated from?
- nuclear pleomorphism and size
- mitotic activity
- necrosis
How is tumour grade usually assessed?
tumour grading is subjective as there are a lot of moderate grades
