*Pathology (4) Flashcards
What is cancer?
Uncontrolled cell proliferation and growth that can invade other tissues (can metastasise)
What is a tumour?
A descriptive word to describe swelling - can be benign, malignant, inflammatory or even a foreign body
What is neoplasia?
“new growth”
Is neoplasia in response to a stimulus?
No - unlike hyperplasia which is
Is neoplasia benign, premalignant or malignant?
Can by either of the 3
Is neoplasia and cancer interchangeable?
No - not all neoplasia is cancerous
What is the only place in the body that has not been reported to have undergone neoplastic change?
The lens of the eye - can occur in any other cell of the body
What is the difference between benign and malignant?
Anything that can spread to other parts of the body is malignant
What is invasion?
What is metastases?
When the cancer cells moves directly into a new part
When the cancer cells break off and migrate to another part of the body
What must an epithelial malignancy invade in order to metastasise?
The basement membrane
What is dysplasia?
Disordered growth
Is dysplasia always cancer?
No but they can become cancer
Is dysplasia in response to a stimulus?
No
Does invasion occur with dysplasia?
No - when dysplasia invades it is called cancer
What are the grades of dysplasia?
Low grade = takes a while to metastasise
High grade = closest to becoming cancer
What are we looking for in cervical smear screening?
Dysplasia
What is carcinoma in-situ?
Is this cancer?
Dysplasia affecting the whole of the epithelium which is confined by the basement membrane (it has not yet invaded)
There is debate to whether this is classified as cancer or not as it has not invaded yet but it is the last stage before invasion
What is metaplasia?
Change from one mature cell type to another usually in response to a stimulus
What metaplasia can occur in the bladder due to having a catheter?
Transitional epithelium to squamous epithelium
Is metaplastic epithelium at risk of undergoing metaplastic change?
Yes
Is hyperplastic tissue at risk of developing cancer?
Yes - if you keep telling something to turn on it can become automatic and no longer require a stimulus
What causes cancer?
Genes (increase risk) Chemicals (e.g. smoking) Alcohol UV radiation Other radiation Drugs Infections Obesity Some have an unknown cause
What are the 4 main groups of genes that cancer cells target?
Oncogenes
Tumour suppessor genes
Spell checkers
Genes that aid in avoiding apoptosis
What are the cell changes that occur with cancer formation?
Dysplasia to carcinoma in situ to invasion =cancer
Are rare tumours or more common tumours easier to find a cause for?
Rare tumours - many cancers are caused by a combination of more than one factor
What is BRCA1 and BRCA2 genes?
Genes that produce tumour suppressor proteins and when faulty can lead to breast cancer
What is a tumour suppressor gene?
a gene whose function is to limit cell proliferation (operate at the cell cycle checkpoints) and loss of whose function leads to cell transformation and tumor growth.
What is an oncogene?
A gene that played a normal role in the cell as a proto-oncogene and that has been altered by mutation and now may contribute to the growth of a tumor.
What does autosomal dominant mean?
Only one copy of a faulty gene is needed for it to have an effect - a single altered copy of the gene is enough to increase a person’s chances of developing cancer.
What is the role of a photo-oncogene?
gene that codes for proteins which promote cell division only when an external signal is received (e.g. wound needs healed)
Is proto-oncogene to oncogene mutation dominant or recessive?
Dominant = only need one mutation for cancer formation
Is tumour supressor gene mutations dominant or recessive?
Recessive as only need one functioning gene to prevent cancer (although patients with one mutation have a much higher chance of having a second hit and developing cancer) - doesn’t seem to always be the case
Is the Rb gene a tumour suppressor gene or an oncogene?
Tumour supressor gene (children with Rb mutation have a 10,000 increased risk of Rb)
Is APC a tumour supressor or oncogene?
Tumour supressor gene
What condition does a mutation in APC cause?
Familial adenomtous polyposis (gardner’s syndrome)
100% chance of bowel cancer before 50 yo
2 examples of autosomal dominant mutations in tumour suppressor genes that increase likelihood of cancer?
Retinoblastoma (Rb mutation)
FAP (APC mutation)
What is the double hit hypothesis?
One working gene is enough - you need 2 faulty copies to have a functional problem = to develop cancer (those who have inherited one faulty copy already have an increased risk of cancer)
What does autosomal recessive mean in terms of cancer genes?
a person has an increased risk of cancer only if he or she inherits a mutant (altered) copy of the gene from each parent
What syndrome does a mutation in p53 cause?
Li Fraumeni (wide range of cancers, early onset, dominant)
What conditions does a mutation in PTCH cause?
Gorlin’s syndrome (basal cell carcinoma)
What condition does a mutation in PTEN cause?
Cowden’s syndrome (increased risk of breast, thyroid and endometrial cancer along with others as well as an increased development of hamartomas)
What is the name of the condition caused by mutations in MEN1 and RET?
Multiple endocrine neoplasia
What 2 conditions can a mutation in MLH1 cause?
HNPCC
Muir Torres syndrome
What is the name of the fungus on peanuts which increases your chances of developing cancer?
What type of cancer does this increase the risk of?
Aflatoxin
Liver
What is the name of the chemical dye which increases your chances of developing cancer?
What type of cancer does this increase the risk of?
Beta-naphthylamine
Bladder
What is the name of the food preservative that increases your chance of developing cancer?
Nitrosamines
What is the name of the chemical that increases your chance of developing cancer?
Arsenic
What type of lung cancer is smoking very strongly associated with?
Small cell lung cancer
What type of cancers does smoking increase the risk of? (4)
Lung
Head and neck
Bladder
Cervical
What is the name of the virus that increases your risk of cervical cancer?
HPV (along with head and neck cancers)
How does UV radiation increase your risk of skin cancer?
Causes formation of pyrimidine dimers in DNA
Initially the cell can repair the DNA damage but eventually with repeated exposure the repair mechanisms are overwhelmed
What type of cancer did patients from Chernobyl get?
Thyroid
What type of cancer did patients affected by the the Japanese atomic bomb get?
Leukaemia
What 2 type of cancers does radiation mainly increase the risk of?
Leukaemia
Thyroid
What is cyclin?
a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes
How does Rb prevent transcription?
It binds to E2F preventing it from switching on transcription
How is Rb prevented from turning off the cell cycle leading to transcription?
Cyclin D/ CDK 4 complex phosphorylates Rb = can’t bind to E2F meaning E2F is free
How can HPV lead to cancer? (2)
It produces E6 which increase destruction of p53
It produces E7 which an oncogene product of HPV
This binds to Rb preventing Rb from binding to E2F switching off the cell cycle
What are 4 examples of cancers that are associated with EBV?
Burkitt-lymphoma
B cell lymphomas
Hodgkin lymphomas
Nasopharyngeal carcinoma
What type of cancers are often associated with chronic inflammation?
Why?
Lymphomas
Constant lymphocyte reproduction may lead to errors in production
What is Schistosomiasis?
What type of cancer does it sometimes cause?
Why?
an infection caused by a parasitic worm that lives in fresh water in subtropical and tropical regions
Squamous cancers of the bladder
Chronic inflammation
What type of cancers does obesity increase the risk of?
Endometrial (cholesterol is analogous to oestrogen meaning stimulates the steroid receptors in the endometrium causing hyperplasia)
Also increased risk of renal cell carcinoma
Is neoplasia always dysplastic?
No, can be benign and not dysplastic, benign and dysplastic or malignant
In terms of mutations, what does dysplasia mean?
Cells have accumulated mutations in sufficient quantity to be identifiably abnormal down the microscope - this is pre-malignant
How does neoplasia become cancer?
It achieves some level of immortality e.g. 1 out of the category of 4 e.g. tumour suppressor gene mutations
What is the enzyme produced by cancer cells that helps it “digest” connective tissue and invade?
Matrix metalloproteinases
What is metastasis?
the development of secondary malignant growths at a distance from a primary site of cancer.
What are the 2 ways that cancer can metastasise?
Through the lymphatics or blood
Why are hepatic metastases relatively common?
A lot of venous circulation enters the liver
How can the unusual spread of prostate cancer to bone be explained?
Different tumours will express different receptors for vessel wall adherence
What is angiogenesis?
Production of new blood vessels
What proteins can tumours produce that allow them to induce angiogenesis (in order to grow their own blood supply)?
Vascular endothelial growth factor (VEGF)
Platelet derived growth factor (PDGF)
How does Bevacizumab work?
What type of cancers is it used to treat?
It blocks VEGF receptor
Cancers reliant on VEGF pathway (advanced bowel cancer, some lung cancers)
How does Imatinib work?
Used to treat?
It is a PDGF receptor inhibitor
Tumours of connective tissues (GI stromal tumours)
Some tumours of the blood (lymphomas and leukemias)
