8 Neoplasia 1 & 2 Flashcards
Define Tumour
Detectable lump or swelling
Define Neoplasm
An abnormal growth of cells that persists after initial stimulus is removed
Define Metastasis
Malignant neoplasm that has spread from its original site to a new non-contiguous site
Define Dysplasia
A pre-neoplasticism alteration in which the cells show disordered tissue organisation
-reversible
How is Dysplasia exhibited microscopically
Pleomorphism
Large hyperchromatic nuclei
High nuclear:cytoplasmic ratio
Describe primary and secondary site in neoplasm
Primary: original location of the malignant neoplasm
Secondary: the place to which the malignant neoplasm has spread
Describe the difference between Benign and Malignant neoplasm in terms of behaviour and histology
Benign:
(B) expansive growth locally, retained original functions of cells
(H) resembles cells of origin, few mitoses, normal in nuclear:cytoplasmic ratio, cells are uniform throughout tumour
Malignant:
(B) expansive, invasive, potential to metastasise, less likely to retain original function, acquire unexpected functions
(H) failure to differentiate fully, abnormal form of mitoses, high nucleus:cytoplasmic, pleomorphism
How is the degree of differentiation classified
Grade is an indicator of differentiation of the cell
High grade = Poorly differentiated
How does neoplasia occur
- Exposure to carcinogens causes non-lethal genetic damage
- Accumulated mutations in somatic cells
- Mutations are caused by initiators (mutagenic agents)
- Promoters cause cell proliferation
- Tumour is formed by clonal expansion of a single precursor cell that has incurred genetic damage
Examples of Initiators
Chemicals (smoking, alcohol consumption, diet)
Infectious agents (HPV)
Radiation
Inherited mutations (BRAC I & II)
What are the four classes of normal regulatory genes
Growth promoting proto-oncogenes
Growth inhibiting tumour suppressor genes
Genes that regulate apoptosis
Genes involved in DNA repair
Describe Proto-Oncogenes and its functions
Function: Involved in signalling pathways and drives proliferation
What can mutation in a proto-oncogene lead to
Conversion to Oncogene and can subsequently activate it to become an Oncoprotein permanently
Functions of Tumour Suppressor Genes.
Stop cell proliferation
What can mutation to Tumour Suppressor Genes lead to
Stop cell proliferation
-causes ‘loss-of-function’
-both alleles must be damaged for transformation to occur
-failure of growth inhibition
Example of Tumour Suppressor Genes
TP53 gene
-codes for protein P53 which directs apoptosis, repair
-‘guardian of the genome’
Function of Apoptosis Regulating Genes
Regulate cell death and survival of cells
Mutation of DNA Repair Genes results in
-loss of function mutations
-impair ability of cell to recognise and repair non-lethal genetic damage in other genes
Mutator phenotype: A stage where affected cells acquire mutations at an accelerated rate
-marked by genomic instability
Pattern/rule in naming Neoplasms
Benign tumours:
ends in -oma
Malignant tumours:
End in carcinoma, sarcoma
Examples of epithelial neoplasm (Benign & Malignant)
Benign:
Squamous papilloma, Transitional cell papilloma, Adenoma, Cystadenoma
Malignant:
Squamous cell carcinoma, Transitional cell carcinoma, Adenocarcinoma
Check table with tissue of origin and its term for benign and malignant tissue
Define Invasion
Breach of the basement membrane with progressive infiltration and destruction of the surrounding tissues
Define Metastasis
Spread of tumour to sites that are physically discontinuous from the primary tumour
Describe the process that leads to metastasis
- Grow and invade at the primary site
- Enter a transport system and lodge at a secondary site
- Grow at the secondary site to form a new tumour (colonisation)
Describe the alteration needed for invasion
Altered adhesion:
-reduction in E-Catherine expression,changes in Integrin expression
Stromal proteolysis:
-altered expression of predates, matrix metalloproteinases (MMPs)
-nearby non-neoplastic cells provides GF and proteases
Motility:
-changes in actin cytoskeleton
What is mesenchymal transition and when does this happen
When cell takes on a phenotype more akin to mesenchymal cell than an epithelial cell
