Pathology part 4 Flashcards by Olivia McNee

Define cancer?

Uncontrolled cell proliferation and growth that can invade other tissues

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What is a tumour?

Swelling
Benign or malignant
Inflammatory or foreign body

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Define neoplasm

New growth not in response to stimulus

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What can neoplasm be?

Benign, premalignant or malignant

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What is neoplasm not

Clinician code for cancer

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Where can neoplasm be

Anywhere apart from lease of eye

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Define malignant

Metastatic potential

Goes beyond basement membrane of epithelium

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Define metastases

Spread to other sites

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what are the precursor legions of malignancy?

Dysplasia
Metaplasia
Even hyperplasia

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What happens to bronchial epithelium in reaction to thermal/chemical injury?

Metaplasia to squamous epithelium from columnar

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What kind of metaplasia occurs in the bladder?

Transitional epithelium to squamous as a result of inflammation from catheters

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How can hyperplasia become autonomous?

No longer require stimulus

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Why are obese people at risk of hyperplasia?

Steroid hormone structure is closely shared by cholesterol

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Define dyplasia

Disordered growth not in response to stimulus

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What is invasion?

Growth beyond the basement membrane

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How is dysplasia graded?

High grade most abnormal and closer to cancer

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What is CIS?

Carcinoma in situ
Dysplasia affecting the whole of the epithelium- applies to non-glandular epithelium

Last stage before becoming invasive

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What causes cancer?

Genes
Smoking 
Alcohol 
UV radiation 
Other radiation
Drugs
Infections
Obesity

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What is a weinberg hallmark?

Specific genes/proteins with specific functions that enable cellular progression to malignancy

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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

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How many carcinogens does smoke contain?

> 40

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Where is aflatoxin found? What does it cause?

fungus on peanuts

p53 mutation

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Where is beta-napththhylamine found?

Chemical dyes

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Where are nitrosamines found?

Food preservative

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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?

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?

1. Receptors with intrinsic tyrosine kinase activity 2. 7 transmembrane G protein-coupled receptors 3. 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