Pathology part 4 Flashcards
Define cancer?
Uncontrolled cell proliferation and growth that can invade other tissues
What is a tumour?
Swelling
Benign or malignant
Inflammatory or foreign body
Define neoplasm
New growth not in response to stimulus
What can neoplasm be?
Benign, premalignant or malignant
What is neoplasm not
Clinician code for cancer
Where can neoplasm be
Anywhere apart from lease of eye
Define malignant
Metastatic potential
Goes beyond basement membrane of epithelium
Define metastases
Spread to other sites
what are the precursor legions of malignancy?
Dysplasia
Metaplasia
Even hyperplasia
What happens to bronchial epithelium in reaction to thermal/chemical injury?
Metaplasia to squamous epithelium from columnar
What kind of metaplasia occurs in the bladder?
Transitional epithelium to squamous as a result of inflammation from catheters
How can hyperplasia become autonomous?
No longer require stimulus
Why are obese people at risk of hyperplasia?
Steroid hormone structure is closely shared by cholesterol
Define dyplasia
Disordered growth not in response to stimulus
What is invasion?
Growth beyond the basement membrane
How is dysplasia graded?
High grade most abnormal and closer to cancer
What is CIS?
Carcinoma in situ
Dysplasia affecting the whole of the epithelium- applies to non-glandular epithelium
Last stage before becoming invasive
What causes cancer?
Genes Smoking Alcohol UV radiation Other radiation Drugs Infections Obesity
What is a weinberg hallmark?
Specific genes/proteins with specific functions that enable cellular progression to malignancy
What is the double hit hypothesis?
one working gene is enough. Two faulty copies to have a functional problem. Those who have inherited one faulty copy already are at increased risk
How many carcinogens does smoke contain?
> 40
Where is aflatoxin found? What does it cause?
fungus on peanuts
p53 mutation
Where is beta-napththhylamine found?
Chemical dyes
Where are nitrosamines found?
Food preservative
What can arsenic cause?
Skin cancer
What are initiators?
long lasting genetic damage. Not sufficient to cause cancer. Must be followed by a promoter
What are promoters?
require initiators to have caused damage. Time period can vary after initiation
Which cancers is smoking associated with?
Lung cancer- small cell
Head and neck cancers
Bladder cancer
Cervical cancer- with HPV
What are polycyclic aromatic hydrocarbons?
Potent carcinogen
Can be present in animal fat from meat
Smoked meat and fish
Which cancers are aflatoxin associated with?
Liver cancer
Where are aflatoxin cancers common?
China
Which cancers are beta naphythylines associated with?
Bladder cancer
Conjugated in the liver with glucuronic acid and therefore not toxic for long
Human urine contains glucuronidase - bummer
What does radiation cause?
Formation of pyrimidine dimers in DNA
Nucleotide excision repair (NER) is eventually overwhelmed
What is xeroderma pigmentosa?
Genetic defect in NER and suffer from numerous skin cancers
Which scans can increase cancer risk?
CT scans
What is the process by which viruses cause cancer?
Microbial carcinogenesis
What is the oncogene product of one of the HPV viruses?
E7
What is the role of E6 oncogene?
Increases destruction of p53
What is the role of E7 oncogene?
prevents retinoblastoma (RB) protein from acting
What is the role of retinoblastoma?
Rb usually binds E2F. When free of Rb, E2F promotes transcription of DNA polymerase etc.
What cancers is EBV implicated in?
Burkitt-lymphoma
B-cell lymphoma
Hodgkin lymphoma
Nasopharyngeal carcinoma
How does chronic inflammation cause lymphomas?
constant lymphocyte reproduction may lead to errors in production
What causes increased risk of hyperplasia in the endometrium
Obesity
CHolesterol analagous to oestrogen
What meat container carcinogens?
BBQ meat
What are sustained growth signals?
Signal cells to get big, grow and not stop
Avoid normal homeostatic controls
What are the three categories of growth receptors?
- Receptors with intrinsic tyrosine kinase activity
- 7 transmembrane G protein-coupled receptors
- Receptors without intrinsic tyrosine kinase activity
What does the EGFR overecpression cause?
carcinomas
What is the BRAF mutation?
Mutation of RAF
Melanoma
COlorectal
What is the RAS mutation responsible for?
lung
Pancreas
Colorectal
Thyroid
What is Myc?
Nuclear transcription factor that promotes growth
What is mutation of Myc common in?
Lymphoma, neuroblastoma, small cell cancer of the lung
What is PI3K mutated in?
Haematological malignancies
What are APC mutations?
One of the most common in colorectal cancer
-can occur as a germline mutation causing an inherited condition FAP and gardeners
What is the role of tumour supressors?
Stop growth
Cells with malignant ambitions must remove them
What is the most commonly mutated protein across all cancers?
p53
What is the roll of p53?
Cell cycle arrest- senses DNA abnormalities at G1 and pauses cell cycle, increases levels of p21 which is a CDK inhibitor
inhibits phosphorylation of Rb
Induces apoptosis if DNA not repaired via BAX pathway
What is CDK activated by?
Cyclins
What is VHL?
Von-Hippel Lindau
Loss of VHL increases level of angiogenic growth factors
What is the role of PTEN?
Increases transcription of p27
What is the role of p27
Blocks CDKs and cell cycle progression
What does CDK so?
Inhibits PI3K/AKT pathway we saw earlier
What happens in malignancy to allow unlimited replication?
Mutation that reactivates telomerase
What is Bcl-2
anti-apoptotic molecule
binds Bax/Bak to stop holes being punched in mitochondria
What is VEGF?
Vascular endothelial growth factor
Up-regulated in some malignancies
Describe BRCA?
Complex genes and proteins
Breast, ovarian, pancreatic tumours
Role in DNA repair and cell cycle arrest at G1/S phase
What are mismatch repair proteins?
Family of proteins responsible for identifying faults in the code – mismatched sequences
When are MRPs abnormal?
Lynch syndrome
commonly develop colorectal carcinomas
How can we find faulty protein expression?
Immunohistochemistry
What do we look for in immunohistochemistry?
frequency of mismatched sequences by analysing microsatellites – segments of repeated DNA code specific to an individual
If the microsatellites are full of errors this is called microsatellite instability and indicates the proteins aren’t working
What is PD-L1?
Programmed death ligand 1
Inhibits T-cell proliferation
Tumour express this to avoid immune system
How do cancers chew up surrounding tissues?
Increase expression of matrix metalloproteinases (MMP)
Cells can then chew there way through surrounding tissues and blood vessels
Is cancer clonal?
No
Single parent yes
Identical children no
What is the most important concept in treatment resistance?
Sub-clones- chemotherapy and targeted therapy may work against certain but not all clones
