L22: Reproductive Cancers Flashcards
What is tumour?
formed by an excessive, uncontrolled proliferation of cells as a result of an irreversible genetic change, which is passed from one tumour cell to its progeny
What is neoplasia?
new uncontrolled growth of cells in the body
What is the difference between benign and malignant tumours?
Benign tumours stay localised at their site of origin (non-cancerous), while malignant tumours are able to invade and spread to different sites (metastasis)
What are malignant tumours features?
Infiltrate, fast growth, large plemorphic nuclei, less differentiated
What is the difference between primary and secondary cancers?
Primary - tumour arise at the primary site from cells normally present there, secondary - metastatic
What is the development and progression of cancer cell?
- cell with mutation (usually able to fix during cell cycle, repair mechanism)
- hyperplasia (expansion of cells)
- dysplasia (morphology starts to change)
- in situ cancer (confined in local area)
- invasive cancer
What causes a cancer to develop?
- loss of tumour suppressor gene function
- gain of oncogene function
- could be: mutagens, pathogens, inactive repair
Which genetic abberations can cause cancer?
- duplication (genome multiplied)
- inversion (DNA twists during S phase)
- deletion
- insertion (happens a lot in leukaemia)
- translocation
What are proto-oncogenes?
Normal version of genes that code for proteins that are needed for normal cell division
What are oncogenes?
Mutated proto-oncogenes, mutations in certain genes promote uncontrolled cell division/proliferation
What are activating mutations?
- Only certain mutations in a proto-oncogene will convert it to the oncogenic form
- activation of (proto-) oncogenes allows cells to bypass the need for extracellular growth signals
What is ‘dominant acting’ in regard to oncogenes?
Only one allele (copy) of a proto-oncogene needs to acquire an activating mutation
How do oncogenes work? What do they code for?
- oncogenes code for:
i) a hyperactive version of the protein product
or
the normal protein product but
i) in abnormal quantities
ii) at the wrong time
iii) in the wrong cell type
What are tumour suppresor genes? what are their examples?
- tetrameric transcription factor
- inhibits cell cycle progression (through p21) - allows for DNA repair
- p53 is inactivated in around 50% of human cancers
What is a dominant negative effect regarding p53?
mutant p53 exerts a dominant negative effect by preventing wild-type p53 from binding to the promoter of its target genes
What is Li-Fraumeni syndrome?
germline mutation, which predisposes offspring to cancer, p53 mutation
What effect does HPV have on p53?
the E6 protein of HPV inactivates p53 in cervical epithelial cells
What are the steps of cancer metastasis?
- mutation
- primary tumour
- vascularization (angiogenesis) - vessels bring nutrients, but also give a root out of the tumour
- detachment (epithelial-to-mesenchymal transition) - mesenchymal cells have different morphology able to move around the body
- intravasation
- extravasation
- invasion
- secondary tumour
- vascularization
What are the routes of metastasis?
- local invasion
- lymphatic spread (important for breast cancer)
- blood spread
- transcoelomic (spreads through cavity, such as peritoneal cavity, as in the case of ovarian cancer)
What are the reasons for increasing survival of breast cancer?
- better awareness
- introduction of screening (thus, incidence is goign up)
- improvements in treatment (deaths are going down)