Neoplasia (1) - LECTURE 16 Flashcards
What is the most common type of cancer?
NON-MELANOMA SKIN CANCERS
then..
breast, prostate
then…
colorectal or bowel cancer, melanoma of lung
What is the definition of NEOPLASIA?
“NEW GROWTH”
- cells that fail to respond normally to signals controlling growth
- cells proliferate excessively
- alterations in cell genomes
CHANGES ARE PERMANENT!
What is the definition of a TUMOUR?
“A proliferation of cells that grow in an UNREGULATED manner, not responding to the normal control mechanisms of the body”
Tumours are the THREE “Ps”
PROGRESSIVE - independent of normal growth factors and continue to grow regardless of requirements
PURPOSELESS - abnormal mass which serves no purpose
PARASITIC - draws nourshiment from the body but does not contribute anything!
What are the 2 Types of NEOPLASMS (TUMOURS)?
BENIGN - no metastatic potential
MALIGNANT - metastastic potential
How do neoplasms arise??
Normally cell proliferation = apoptosis
BUT with neoplasia cell proliferation > apoptosis
Which cell is a neoplasm more likely to arise?
a. epithelial cell?
b. hepatocyte?
c. neuron?
= A
Epithelial which is dividing all the time = has a high rate of mitosis
What two processes are disrupted in the development of a neoplasm?
= INCREASE CELL PROLIFERATION
AND
DECREASE APOPTOSIS
So what actually causes the derangements in cellular proliferation?
There are GENETIC MUTATIONS every time a cell divides.
SOMETIMES there are mistakes made (often caused by CACINOGENIC AGENTS (diet, radiation, smoking, HPV) or CHRONIC INFLAMMATION)
So why isn’t neoplasia more common?
Cell proliferation is TIGHTLY regulated normally!
- normally checked by…
PROTO - ONCOGENES
Proto - oncogenes - what are they?
Usually present in normal cells
They ENCODE proteins that promote normal cell growth and proliferations.
GENETIC ALTERATIONS can alter the transcription of proto-oncogenes or the behaviour of their products leading to abnormal proliferation
Need to affect TWO ALLELES TO HAVE AN IMPACT
Proto-oncogenes - What happens when they mutate?
Three things can happen causing cell proliferation
1. Point Mutation (Colon and breast)
2. DNA Amplification (breast, ovarian gastric)
3. Translocation (breast, lymphoma)
What are Tumour Suppressor Genes?
Present in normal cells and apply the BRAKES to normal cell proliferation
commonly control apoptosis, DNA repaie and allow cells to pass through checkpoints
Mutations need to happen in both copies of genes to have an affect.
Inheriting a Proto-oncogene or TSG?
Normally of you inherit a PO die before birth
TSG can appear later
Difference between SOMATIC and GERMLINE mutations
Simatic - occur in nongermline tissues and cant be inherited
Germline - Present in egg or sperm and can be inherite
Problem Question:
A gene codes for a proteing which involves the apoptotic pathway in response to DNA damage.
Is this a TSG or PO?
A TSG - BRAKES
Problem Question:
When switched on RAS protein activates other proteins which turns on genes involved in cell growth and proliferation.
Is this a TSG or PO?
= PO - cell growth
Can one mutation usually cause cancer?
No not normally.
In order for neoplasia to develop - multiple mutations usually occur in multiple PO and TSG
How do genetic mutations lead to neoplasia?
Single cell gains a mutation –> multiple mutations –> increase cell proliferation
OR gained over time..
promotion of angiogenesis –> production of factors that can breakdown basement membrants –> can metastises
Molecular changes of neoplastic cells and their phenotypic behaviour is constantly evolving process can result in additional genetic abnormalities
What are the SIX KEY FEATURES OF NEOPLASM?
- self sufficiency in growth signals
- insensitivity to growth inhibitory signals
- evasion of programmed death
- limitless replications potential
- sustained angiogenesis
- tissue invasion and metastasis
These genetic mutations happen over time..
How - what are the steps?
Many invasive carcinomas are throught to arise as a result of progression and invasion of pre-existing epithelial dysplasia
NORMAL —DYSPLASIA – IN SITU CARCINOMA – METASTASIS
Note can go NORMAL – METAPLASIA – NORMAL
or
NORMAL – METAPLASIA – DYSPLASIA etc
(metaplasia e.g. Barrett’s Oesophagus or Smoking changes cells but can revert back once stimuls is removed)
What is DYSPLASIA?
Disordered growth and maturation of the cellular components of a tissue
Found in epithelia
loss of uniformity of individual cells and their architectual organisation
pleomorphic cells
mitotic figures
LOOK FOR - cells are NOT organisaed
BUT VIP NOTE THAT THIS CAN STILL BE REVERSIBLE!!
Dysplasia - so when does it become irreversible?
Mild dysplasia ———->>>Severe Dysplasia/Carcinoma in situ
Dysplasia shares many forms of cancer and the line betweeen them is still unclear.
It does NOT indicate cancer and does not necessarily progress to cancer BUT it can be a pre-neoplastic lesion
When dysplastic changess are marked and involved THE ENTIRE THICKNESS OF THE EPITHELIUM = A CARCINOMA IN SITU which IS a pre-invasive stage of cancer.
In Situ Carcinoma
- LOCALIZED groeth confined to the epithelium
Pre-invasive stage of cancer
- cells CANNOT penetrate the basement membrane
BUT if left to acquire further mutations one of these mutations may allow it to penetrate the basement membrane and acquire the ability to become INVASIVE
