Neoplasia and tumour biology Flashcards
What are all the different growth disorders during life?
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What does a normal cell cycle look like? (draw it)
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How does cell proliferation occur?
Growth factors
growth factor receptors
transduction
translation
cell cycle proteins
When are the proto oncogenes and tumour suppressor genes involved?
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What are proto oncogenes?
They are the pre form of oncogenes before they are switched on. When they mutate usually they then become oncogenes.
Can you name some oncogenes?
RAS- involved in kinase signalling pathway- regulating cell growth and differentiation
Src- regulates cell activity
What are tumour suppressor genes?
They suppress the tumour at various stages in the cell cycle. This coupled with proto oncogenes is the two hit hypothesis being both need to mutate in order for a tumour to occur.
Can you name some tumour suppressor genes?
p53: a transcription factor that regulates cell division and cell death
Rb: alters the activity of transcription factors:::::: side note::::
need to overcome passive and active regression.
rb involved in G0-G1 phase of the cell cycle HDAC etc. research
APC: controls the availability of a transcription factor.
Why is p53 so important?
P53 can arrest the cell cycle and send cells into apoptosis. This is important if the cells are going into tumours cells as this could be dangerous and it would need to be stopped.
Can you summarise the molecular determinants of cancer?
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What is the first step in tumour genesis?
Initiation: Introduction of irreversible genetic change into cells by action of mutagenic intiator.
But have mutations which give them growth advantage. Could be resistant to apoptosis inducing stimuli.
What is the second step in tumour genesis?
Promotion: Initiated cells exposed to certain stimuli, which alter gene expression and creates an envrionment which promotes cell growth.
May lead to pre neoplastic lesion of benign tumours
Promoters are non mutagenic their effects can be reversible.
What is the third step in tumour genesis?
Progression: Includes conversion of benign tumours into metastatic ones.
Malignant conversion irreversible
complex poorly understood procedure
increasingly tumour cell heterogenity
Can you show all three steps of tumour growth in a diagram?
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What are the 6 hallmarks of cancer?
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What would the pathologist describe if analysing a neoplastic lesion?
Cell and nuclear characteristics
Mitotic index
Signs of invasion or metastasis
margins
Other features- connective tissues etc. ground substances and ulceration
When proliferating what determines how a benign tumour grows and how a metastatic tumour grows?
Benign tumour will tend to grow by expansion and compression.
Malignant tumour will tend to grow by local invasion
What is tumour angiogenesis?
Tumours induce host vessels to supply, branches by production of tumour angiogenesis factors.
Tumour lymphangiogenesis similar.
What are the routes of metastasis?
Local invasion
Intra vascular blood or lymphatic
serosal spread
intra organ seeding
Can you draw a diagram of the metastatic cascade
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What does OPA stand for?
Ovine pulmonary adenocarcinoma which is a cause of chronic respiratory disease in humans.
What type of virus is OPA?
Beta retrovirus
Can you draw a diagram of retroviral replication?
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How can you detect whether this OPA is targetting b or t cells?
IHC. Staining particular b or t cells. For B cells it is most likely CD38 and for t cells it is most likely CD3.
Can you show a diagram with the pathogenesis of OPA?
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Why is identification of the target cell important?
- improve the understanding of the early stages of OPA pathogenesis in sheep.
- Improve the use of OPA as a model to bronchioloalveolar carcinoma (BAC)
What goes into the pathology report when describing the neoplasm?
Subgross description
Patterns of cells and type of stroma
The cells
mitotic activity
unique features
evidence of malignancy
clean up
How would you describe this?
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squamous cell carcinoma: nests, packets and cords of polygonal shaped cells
What is tumour grading?
Determines cellular morphology most accurate predictor of tumour behavior. Grading can be based on behavior, invasiveness, mitotic index, necrosis and overall cellularity
What are the main sub divisions for tumour grading?
Mast cells
Mammary gland
Soft tissue sarcomas
Synovial sarcomas
Lymphomas
What is vimentin and cytokeratin and what do they do?
Markers for IHC. They can help distinguish a tumour if it from epithelial origin or mesenchymal origin. Cytokeratin is epithlial +ve. Vimentin is mesenchymal +ve.
What markers can you use for round cell tumours?
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What is a mast cell?
Normally present in low numbers in the tissue.
Cytoplasmic granules containing bioactive substances.
Granules are heterochromatic hence the use of various stains.
Involved in type 1 hypersensitivity which is usually allergens.
Are mast cells common and are any breeds disposed to them?
Yes common tumours, 16-20% of all tumours are mast cell in dogs! Most dog breed so the boxer, etc. Typically in 7-9 year old dogs. HOwever some breeds can have more aggressive mast cell tumours than others.
What is the growth fraction?
The relative number of cells actively involved in cell cycle growth at that one point in time.
What is generation time?
Rate of cell proliferation or cell doubling in vivo.
How do you calculate cellular prolfieration then?
growth fraction x generation time OR
Ki67 x AgNor score.
What can mast cell tumours (cutaneous) be differentiated into?
Mastocytic- Well differentiated
-pleomorphic
Histiocytic- (poorly granulated)
Are there any prognostic tests for mast cell tumours?
Yes, KIT and C-KIT test.
KIT is the protein and is found as a receptor on mast cells. Ligand is a stem factor of KIT. Activation via ligand binding promotes cell survival, proliferation and differentiation.
C-KIt is the encoding gene.
Determinant whether mast cells have mutated and overall prognosis of the patient. Especially when it comes to determining the time of spread etc.
