Neoplasia Flashcards
What is oncology?
The study of tumours and neoplasms.
What is a benign neoplasm?
An abnormal growth of cells that persists after the stimulus has been taken away, but does not spread and invade other sites - it remains localised.
What can dysplasia exhibit, microscopically?
Pleomorphism.
Hyperchromatic nuceli.
Large nuclear to cytoplasmic ratio.
How can the functions of neoplasms, relating to their tissue of origin be used to determine its ability to spread to distant sites?
If it has a function that is closely related to its tissue of origin, then it is more likely to be benign.
If its function is severely different to its tissue of origin, then it is more likely to be metastatic.
What does it mean for a tumour to be monoclonal?
The cells within the tumour have all been derived from one precursor cell that has incurred genetic damage.
What genes can be affected to facilitate proliferation?
Growth promoting proto-oncogenes.
Growth inhibiting tumour suppression genes.
Genes regulating apoptosis.
Genes involved in DNA repair.
How could proto-oncogene mutations form a neoplasm?
They usually stimulate the cell to continue within the cell cycle, driving proliferation.
Mutations usually increase or gain functions.
A mutation can form an oncogene which can be transcribed to form an oncoprotein, which can stimulate the cells to continue proliferating.
Dominant so requires 1 mutation.
How can a mutation in a tumour suppression gene form a neoplasm?
Normal function is to inhibit cells from continuing in the cell cycle, preventing proliferation.
A mutation is usually a loss of function.
This facilitates the failure to inhibit growth, allowing the cells to continue to proliferate.
Recessive so requires 2 mutations.
How can a mutation in an apoptosis regulating genes form a neoplasm?
These usually stimulate cells to undergo apoptosis.
Mutations can result in enhanced survival of cells.
How can a mutation in DNA repair genes form a neoplasm?
These usually stop the cell cycle and send the cell into G0, stimulating their repair via DNA repair mechanisms.
Mutations in these are usually loss of function mutations.
They inhibit the cells ability to recognise and repair genes, allowing them to acquire mutations and not be repaired - furthering progression.
It is a state referred to as mutator phenotype, showing genetic instability.
Define invasion.
The breach of the basement membrane with progressive infiltration and destruction of surrounding tissues.
Define metastasis.
The spread of a metastatic neoplasm to distant sites within the body, that are discontinuous from the primary tumour.
Which bones do metastatic bone diseases usually occur in, and what can the signs and symptoms be?
The axial skeleton.
They can be asymptomatic but it is usually painful.
They can often be seen with fractures, or under X-rays as osteolytic lesions or osteoscelortic metastases.
What are osteolytic lesions?
They are areas of a decrease in bone density due to the destruction of bone tissue.
What are osteosclerotic metastases?
They are areas of increases in bone density due to increased production of disorganised bone.
How are tumours usually recognised by the immune system, and how can they evade the immune system?
They are recognised as non-self cells and presented to CD8+ T cells by APCs MHC Class I molecules.
This stimulates the formation of cytotoxic T cells which destroy the tumour cells.
Immunosuppressed patients have a weakened formation of cytotoxic T cells.
They can evade the hosts immune system by:
- The loss or reduction of the expression of MHC molecules.
- Expression of certain factors, from the tumour cells, that suppress the immune system.
- Failure to produce a tumour antigen.
What is the most common paraneoplastic syndrome, and what are the processes for its formation?
Hypercalcaemia.
Osteolysis, induced by primary bone lesions or secondary metastases.
Production of calcaemic humoral substances by extraosseous neoplasm - hormones.
What is SIADH, where does it occur from, and what is the primary sign?
Syndrome of inappropriate ADH secretion.
Commonly from small cell lung cancer.
Hyponatraemia.
What are some miscallaneous symptoms of neoplasms?
Peripheral or cerebral neuropathies.
Skin problems - pruritis or abnormal pigmentation.
Fever.
Clubbing.
Myositis.
Hypoglycaemia.
What causes Li-Fraumeni syndrome, and what types of cancer can there be an increased risk of?
A mutation in the TP53 tumour suppressor gene - loses control over when the cell divides.
Breast and bone cancer.
Brain tumours.
Adrenal gland carcinoma.
Who is eligible for genetic testing?
Strong family history of cancer.
An inherited faulty gene that has been detected in a relative.
What does a positive genetic test mean?
It means that there is a mutation within a gene that increases the risk of a cancer, but does not mean that they have cancer or will necessarily mean that they will develop cancer.
What are the advantages of genetic testing?
Advantages:
- Lifestyle modifications can be made to decrease the risk of a cancer developing.
- Can help prepare a person for if a cancer will develop.
- Medications can be taken to reduce the risk of developing some cancer types.
- Have regular screening to detect the cancer at an earlier stage.
- Can be educated about the signs and symptoms for the development of certain cancers they are predisposed to, to detect the cancer at an earlier stage.
- Can have risk-reducing surgery.
What are the disadvantages of genetic testing?
It can cause unnecessary stress and anxiety as they may never develop the cancer.
The surgery/ medication taken to decrease the risk of developing the cancer can have a negative effect on their health.
Can increase life-insurance cost.
Can children undergo genetic testing, and for what cancers MAY this be beneficial for?
Those that are under 18 are not usually allowed to undergo genetic testing, unless they have consent from the parents and want to have it, they are mentally capable of making the decision, and they understand the benefits and risks of being tested.
It may be beneficial for cancers that develop before the age of 18, such as retinoblastoma.
How does HPV cause cancer, and what type of cancer is it linked to?
The virus invades the cell and utilises the cell’s DNA machinery to make more virus particles.
It synthesises E6 and E7 proteins.
The E6 protein inhibits p53 proteins, which mean that the cell no longer undergoes apoptosis.
The E7 protein inhibits retinoblastoma proteins, which allows the cell to continue in the cell cycle.
It is linked to cervical cancer.
Is there a method of preventing HPV?
The HPV vaccine, which is given to 11-13 year old children.
What does the retinoblastoma gene do?
It is a tumour suppression gene, which the protein formed from it inhibits the cell from continuing within the cell cycle.
It does this by inhibiting the cell from moving through the G1/S cell cycle checkpoint.
What is the RAS gene and what does it do?
The RAS gene is a proto-oncogene.
When activated, via the binding of growth factors, the G-protein then stimulates the production of cyclin D1, which activates CDK, which phospohrylates RB proteins, to allow cells to move past the G1/S checkpoint.
It is seen to be mutated in 90% of pancreatic adenocarcinomas.
What do proto-oncogenes encode?
Growth factors.
Growth factor receptors.
Plasma membrane signal transducers - RAS.
Intracellular kinases - BRAF.
Transcription factors.
Cell cycle and apoptosis regulators.
What is Xeroderma Pigmentosa, and what can it cause?
It is an autosomal recessive disease.
Two mutations in one of the 7 DNA nucleotide excision repair genes.
Most frequently causes skin cancer, due to the sensitivity to UV light.
What is Lynch Syndrome/ Hereditary Non-Polyposis Colon Cancer (HNPCC) syndrome?
It is an autosomal dominant disorder.
Genetic mutation in the DNA mismatch repair genes.
Associated with colon cancer, usually before the age of 50.
What are the 4 proteins involved in mismatch repair?
MSH2.
MSH6.
MLH1.
PMS2.
What is familial breast carcinoma?
It is a mutation in one of the BRCA1 or BRCA2 genes.
Leads to a deficiency in the repair of double strand DNA breaks.
It can also be found in sporadic malignant neoplasms.
What is cancer-specific survival and relative survival?
What do the terms cured and remission mean?
Outline the adenocarcinoma sequence of colon cancer.
