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2. Foundations of Medicine PoD > Tumour Pathology > Flashcards

Tumour Pathology Flashcards

1
Q

Ecotoderm

A

1 of 3 layers formed during embrionic development. Outermost: skin, neurons, mekanocytes

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2
Q

mesoderm

A

1 of 3 layers formed during embrionic development. Middle: muscle, blood, bone, cartilage, endothelium, serous membranes

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3
Q

Endoderm

A

1 of 3 layer formed during embrionic development. Innermost: lining of ariways, lining of gut, glands

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4
Q

mucosa

A

combination of epithelium and CT

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5
Q

Hyperplasia

A

Inc in size of organ due to inc in number of cells

hyperplasia metaplasia and dysplasia reversible because of a stimulus

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6
Q

Hypertrophy

A

an increase in the size of an organ due to an increase in the size of cells - may be physiological or pathological, reversible when stimulus removed

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7
Q

Atrophy

A

Dec in number and/or size leading to dec organ size - pathological or physiological

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8
Q

Metaplasia

A

Complete transformation of one differentiated tissue/cell type into a different differentiated cell/tissue type

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9
Q

tumour

A

Any swelling of any sort, but usually refers to a neoplasm (but could just be swelling process), can be benign or malignant (or inflammatory)

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10
Q

neoplasia

A

An abnormal growth of tissue due to uncoordinated proliferation, it persists even after cessation of the stumuli

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11
Q

Benign neoplasm

A

neoplasm that does not invade or metastasise (spread elewhere in body)

For ex. benign tumour in epithelium would be confined by the basement membrane it sits on (won’t invade CT)

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12
Q

Cancer

A

A non-specific, non-technical term for a malignant neoplasm

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13
Q

benign tumours in the epithelium (names)

2

A

adenoma, papilloma

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14
Q

carcinoma

A

a malignant tumor that occurs in epithelial tissue e.g. adenocarinoma, squamous cell carcinoma

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15
Q

sarcoma

A

malignant tumor of connective tissue e.g. leiomyosarcoma, osteosarcoma, liposarcoma, fibrosarcoma

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16
Q

leukaemia

A

cancer of white blood cells e.g. acute myeoloid leukaemia, acute lymphoblastic leukaemia

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17
Q

Lymphoma

A

malignant tumor of lymph nodes and lymph tissue/ lymphoid cells e.g. hodgkin’s lymphoma

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18
Q

malignant tumour

A

cancerous, fast-growing, spreads easily

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19
Q

what are not all “oma”???

A

neoplasia (granuloma is inflammatory)

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20
Q

Summary venn diagram

A

see sheet ;)

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21
Q

Give the features of benign and malignant tumours (e.g. growth rate, shape, treatment recurrence…)

A

see sheet ;)

Key LO so revise it

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22
Q

How does a benign tumour compare to a malignant one under the microscope?

A

Benign = round and “normal”
Malignant = uneven, unsymetrical, broken, not whole

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23
Q

benign neoplasm of bone

A

osteoma

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24
Q

General rule when identifying benign and malignant neoplasms

A

Benign = ends in oma
Malignant = ends in sarcoma

lymphoma is exeption - it is malignant and not benign

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25
Q

physical properties of cancer cells

A
  • Pleomorphic - all different sizes/shapes to each other
  • Hyperchromatic - nucleus dark blue when stained
  • Coarse chromatin - DNA wound in course/lumpy way
  • Highly mitotic and abnormal forms - divide in unregulated manner
  • Disorganised structure
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26
Q

How does the behaviour of cancer cells compare to that of normal cells

A

Cancer:
* unregulated growth
* Loss of cohesion
* Immaturity
* Immortality

Normal Cells:
* Replicate when required
* Stick together and stay put
* Specialise to a specific role
* Die when instructed

Learn cancer behaviour

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27
Q

10 steps

A
  1. Avoid immune destruction (hide markers from immune system)
  2. Enable replicative immortality - keeps replicating (ignores telomeres)
  3. Activate invasion and metastasis - spread and looses ability to stick together
  4. Induce angiogenesis - make new blood vessels to supple tumour
  5. Resist cell death (like 2) - stop apoptosis
  6. Deregulate cellular energetics - put all energy to growth and spread (even in hypoxic environments?)
  7. Sustain proliferative signaling - makes pathway keep going without need for molecule to start process
  8. Evade growth suppressors
  9. Possess genome instability and mutation - survival of fittest –> clonality
  10. Mediate tumour-associated inflammatory response (stops inflammatory response)

shee sheet for diagram

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28
Q

carcinogenesis

features? and definition

A
  • Tumour angiongenesis
  • Apoptosis
  • Necrosis
  • Proto-oncogene, oncogene, tumour suppressor

Initiation of cancer formation

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29
Q

Tumour angiogenesis

A

The proliferation of a network of blood vessels which supplies a tumor with a supportive microenvironment rich with oxygen and nutrients to sustain optimal growth.
Also an escape route…

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30
Q

Apoptosis

A

Programmed (regulated) cell death, active process.

Cells splits into fragement all still contained by a cell membrane.

Happens in organised manner with energy often being required to intitiate

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31
Q

Necrosis

A
  • Premature (unregulated) cell death
  • A passive process
  • Toxic cell contents leaked into extracellualr compartments
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32
Q

Define/explain:
* Proto-oncogene
* Oncogen
* Tumour suppressor

A
  • Proto-oncogene: group go genes with normal function in cell growth/development but can mutate and cause cancer
  • Oncogen: cancer causing, mutated form of proto-oncogene
  • Tumour suppressor: (e.g. p53) stops cancer, but when mutated, does so ineffectively
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33
Q

Explain/summarise the spread of cancer (metastasis)

A
  • Metastatic spread is the major clinical problem; ultimately causes death in many cancers
  • Leads to extracellular matrix remodelling and loss of cell-to-cell and cell-to-matrix adhesion
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34
Q

How do cancers spread (metastasis)?

4

A
  • Local spread (tissue next to cancer)
  • Lymphatic spread
  • Haematogenous spread
  • Trans-coelomic spread (within organ cavity)
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35
Q

Metastasis: lymphatic spread

A
  1. Invade connective tissue
  2. enter lymphatic
  3. travel through lymphatics
  4. exit lymphatics
  5. enter lymph node
  6. grow in lymph node

each step requires mutations in cancer cells (since normal cells lack these abilities)

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36
Q

Metastasis: trans-coelomic spread

A
  • method by which cancer can spread to a distant site, without having developed the capacity for vascular space invasion
    -spreads through body “cavity”- peritoneal (gastric, colonic, ovarian etc..), pleural (lung)
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37
Q

potential sites of metastasis

not sure if need to know

A

liver, lung, brain, bone, adrenal gland, omentum/peritoneum

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38
Q

What is it important to remeber about cancer occuring in certain sites

A

primary sites often always travel to same secondary site:

e.g. liver (from colorectal), bone (from breast, prostate), omentum/periotoneum (from ovary)

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39
Q

Vascular invasion

A

Also known as blood and/or lymph vessel invasion, is the presence of tumor cells within the lumen of blood and/or lymph vessel, producing circulating tumor cells

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40
Q

local effects of benign tumours

A

Cause obstruction or pressure effects as a result of their mass filling a space or pushing on adjacent structures.
Could be serious if this occurs in an enclosed space (such as within the skull)

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41
Q

local effects of malignant tumours

A
  • Can cause pressure or obstruction
  • As they are infiltrative, they can also destroy nearby tissue, usually leading to inflammation and its consequences (pain, swelling, loss of function etc)
  • Depending on what structures are adjacent to the tumour, this could also lead to bleeding, infection, fractures etc
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42
Q

local effects of tumours in different body parts

(more general knowledge)

A
  • brain= confusion, coma, seizure
  • colon= haemorrhage, constipation, diarrhoea
  • bone= pain, anaemia, fracture
  • lung= haemoptysis, dyspnoea
  • liver= jaundice, coagulopathy
  • spine= parasthesia, paralysis
  • side effects= hair loss, fatigue, immunosuppression
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43
Q

direct/local effects of cancer

Learn - LO

A
  • pain
  • Loss of function
  • haemorrhage
44
Q

distant/systemic effects of cancer

Learn -LO

A
  • Deep Vein Thrombosis
  • paraneoplastic syndrome
  • cachexia (unexplained weightloss)
45
Q

cachexia

(systemic effect of cancer)

A
  • weakness/wasting due to chronic illness
  • can’t necessarily be fixed by increasing nutrition
  • usually muscle loss > fat loss
46
Q

paraneoplastic syndrome

(systemic effect of cancer)

A
  • Some tumours abnormally or inappropriately produce hormones
  • These hormones have systemic effects
    -ADH (anti-diuretic hormone) causes retention of water
    -ACTH (adrenocorticotrophic hormone) causes adrenal gland to secrete excess cortisol
    -PTH (parathyroid hormone) causes hypercalcaemia
47
Q

How can we cure some cancer types before the cancer becomes established

A

by detecting precancer lesions

48
Q

Dysplasia

A
  • disordered cell growth
  • Doesn’t invade
  • Due to genetic changes and characterised by morphological features
  • Is benign but has potential to become cancerous (progress to neoplasia/malignancy) - pre-cancer
49
Q

Histology of dysplasia

A
  • may be variation in nuclear size/shape
  • increased mitotic activity
  • abnormal mitotic forms
  • cells often appears immature and irregular down the microscope
50
Q

term for pre-cancer

A

dysplasia

51
Q

Do all dysplasia form cancers

A

No, not all will become malignant

52
Q

What can benign cancers cause

overview of them (not specifics)

A

Symptoms, pain, death

53
Q

What does the cervical screening programme look for

A

pre-cancer (cervical dysplasia) almost always cause by HPV virus

54
Q

intraepithelial neoplasia

A

A condition in which abnormal cells are found on the surface of or in the tissue that lines an organ, such as the prostate, breast, or cervix - is a pre-cancer (dysplasia)

55
Q

Briefly summarise process of ligand binding

(signal transduction)

A
  1. Ligand attaches to receptor
  2. Changes receptor’s shape on inside part of receptor
  3. Changed inside part of receptor recruits a molecule
  4. The messenger molecule can be activated and released and travel to its target in the cytoplasm/nucleus
  5. These are sometimes called signal transduction molecules and can be part of a chain of molecules
56
Q

Give an example of a signal transduction molecule

A

BRAF

57
Q

What does a T or arrow mean with regards to signal transduction

A

T = downstream molecule inhibited
Arrow = downstream molecule activated

58
Q

How is activation/inhibition of a target molecule usually achieved

A
  • Changing molecule shape

OR
* Adding another molecule (e.g. a phosphate group)

59
Q

What are signalling molecules that go to the nucleus called

A

Transcription factors

60
Q

transcription factors - function/signalling pathway

A
  • Bind to segments of DNA called promotors
  • Can inhibit/activate transcription of the gene by recruitment of the enzyme which transcribes DNA into RNA
  • In reality much more complex, includes
  • transcribed gene which eventually gets turned into a protein
  • DNA sequence which is the promotor
  • Lots of other DNA sequences which help control the gene

Last 2 known as regulatory sequences

61
Q

Quickly summarise the cell cycle

A
  1. G1 - many cells sit here
  2. Then point of no return called restriction point/G1 checkpoint beyond chich cell commits to cell cycle and no longer needs growth factors
  3. some cells exit cycle at G1 (e.g. neurons)
  4. S phase when synthesis of DNA occurs
  5. G2 is 2nd growth phase - period of rapid cell growth before mitosis
  6. G2-M checkpoint - stops cell cycle if there is any DNA damage
  7. M phases- mitotic phase where cellular division occurs
62
Q

growth factor molecules

A

-growth factor molecule (ligand) binds its specific receptor (growth factor receptor) and sets off signal transduction pathway
-effect; push the cell along G1 towards restriction point but not needed beyond restriction point

63
Q

G1 restriction point

how can you progress, what does it act as?

A
  • restriction point at molecular level involves phosphorylation of a protein
  • Numerous phosphate groups required to be present for cell to progresses through rest of G1 and rest of cell cycle
  • acts as a gateway which stops cell cycle progression in ‘bad’ circumstances, such as when the cell is starved of nutrients
64
Q

Phosphorylation - how does it work to allow continuation through the cell cycle

of protein at G1 restriction point

A
  • Varies with numerous inputs from cell signalling molecules and enzymes (some promote and others inhibit phosphoprylation)
  • protein (Rb) with only a few phosphate groups binds a transcripton factor called E2F (normal state of protein is active when it can bind E2F)
  • E2F cannot function if it is bound
  • when numerous phosphate groups added to protein it changes shape and releases E2F molecules (protein= inactive because cannot bind E2F molecules)
  • E2F molecules then bind various target DNA regulatory sequences (e.g. promotors) and cell cycle goes ahead
65
Q

cell progression at G1 restriction point

features

A
  • Once restriction point is passed the whole cell cycle tends to take off and go to completion
  • Cell cycle progression said to be independent of growth factors
66
Q

what is the protein “switch” that controls the restriction point called

A

Restinoblastoma gene product (Rb)

67
Q

Restinoblastoma gene product (Rb)

A
  • normal protein which can go wrong in cancer if mutated
  • Rb gene product and restriction point= central area where many cell cycle genes interact
  • growth factor molecule sets off pathway of molecules which can end up with phosphorylation of Rb gene product
68
Q

What do growth factor molecules set off

A

pathway which ends up with phosphorylation of Rb gene product

69
Q

What does Rb act as in its normal unphosphorylated (active) form

A

tumour suppressor gene as it blocks progression of cell cycle from going ahead

70
Q

what inputs other than growth factors (promotors) are required for G1 progression

phosphorylation of Rb gene promotors

A

Glucose levels, AA/growth factor levels both high

lots of nutrients and growth factors

71
Q

what is required to inhibit progression past G1 other than a lack of growth factors

phosphorylation of Rb gene inhibitors

A

Lack of nutrients (e.g. glucose)

although, lack of either would inhibit

72
Q

What affects phosphorylation of the retinoblastoma gene product

A

multiple inputs; progression only happens when there are lots of nutrients and growth factors

73
Q

HER-2

inactive growth factors - function/what happens

A

Sometimes cells have inactive growth factor receptors that come together to form the active receptor when the growth factor binds- this activates the pathway e.g. HER-2

74
Q

what happens when there is damage to DNA?

what molecule is activated and what does it do

A

-damage increases p53 (transcription factor)
-this blocks (via other molecules) formation of phosphorylates Rb gene product
-therefore G1 blocked from progressing
-p53 also blocks G2-M checkpoint

75
Q

general/normal function of p53

A

stop cells dividing when they have damage to DNA

76
Q

how is DNA damage repaired?

A

-mismatch repair genes - eg** MLH1 gene** - the product of this gene (along with many proteins) helps recognise and replace DNA base mismatches
-MLH1 induces p53 which stops the cell cycle

77
Q

function of proto-oncogene

A

to promote the cell to go through the cell cycle e.g. growth factor

78
Q

how does an oncogene go wrong in cancer?

examples

A
  • Mutations - that increase the amount of oncogene product - for instance a growth factor receptor that is increased in amount - HER-2
  • Mutations - that allow the protein product to work independently of its control mechanism - for instance a signal transduction molecule that continues to work all the time (always in active form) - BRAF
79
Q

Tumour-suppressor gene definition/function

A

gene that regulates cell division - tend to control/block proto-oncogenes

80
Q

One way an oncogene could cause cancer

A

when a growth factor receptor protein has a mutation that means it is overexpressed

81
Q

How can tumour suppressor genes cause cancer

A
  • Cause cancer when have mutations/environmental factors that inactivate them
  • mutation can cause them to loose their function —> cancer
82
Q

how does a tumour-suppressor gene go wrong in cancer?

A
  • Mutations - that stop the protein product from working - for instance- the retinoblastoma gene product
  • Environment - for instance a viral protein binds the protein product and stops it working - p53
  • Mutation - that stop a protein working - eg the MLH1 mismatch repair protein
83
Q

Inherited causes of carcinogenesis

A
  • inherited from parent with abnormal gene
  • can sometimes be due to “de novo” mutatuion in the germ cell of the testes/ovary
  • ex inc. restinoblastoma (malignant tumour of eye) - autosomal dominant
84
Q

environmental causes of carcinogenesis

A
  • Chemicals (eg: smoking, alcohol)
  • Radiation (eg: UV)
  • Infection (eg: human papilloma virus)
  • Other
    All increase the risk of damage (eg breaks, or mutations) to DNA
85
Q

multistep nature of carcinogenesis

A
  • typically need multiple genes to be abnormal
  • may be involved in formation of precancer, invasion locally, expansion of tumour, invasion into vessels, survival at distant sites, avoidance of cell death - so very complex
86
Q

what can go wrong with HER-2 in breast cancer

A
  • mutation= can get overexpression of HER-2
  • therefore receptor can bind more growth factors
  • this makes it much easier for pathway to be upregulated and pushes cell cycle (G1) forwards
87
Q

BRAF

A

signal transduction molecule, proto-oncogene

88
Q

what can go wrong with BRAF in malignant melanoma

(skin cancer)

A

-most common mutation in BRAF in malignant melanoma changes a glutamic acid for valine at amino acid number 600- switches the BRAF on all the time and pushes cell cycle forward
-BRAF V600= oncogene

89
Q

What can cause the BRAF mutation

A

can be hereditary or environmental (e.g. sunlight damaging skin)

90
Q

what can go wrong with the Rb gene product in Rb

A
  • normally have 2 copies of Rb gene making Rb gene product
  • in hereditary cases mutation causes one gene to stop producing protein - but still leaves other gene producing protein but if another mutation, protein is lost from cell
  • E2F molecules are released and can progress the cell cycle
  • then Rb malignancy (of the eye) can occur
91
Q

how can MLH1 go wrong in colon cancer

A

mutation in MLH1 can cause reduction in the amount of its protein-> decreased mismatch repair-> mismatch of base pairs of DNA remains-> when mutation remains and is then replicated and then repaired again all sorts of damage ensues e.g. enzyme that replicated DNA may slip, cell starts to accumulate mutations as it divides-> colon cancer, MLH1 mutations can be inherited (increased risk of colon cancer)

92
Q

smoking increasing risk of cancer

p53

A

numerous chemicals in cigarette smoke-> metabolised to carcinogens in liver-> released into circulation-> damage DNA-> numerous mutations eg mutations in p53

93
Q

radiation increasing risk of cancer

p53

A

sunlight UV radiation lands on the top part of the bottom of the lip of the mouth-> mutations in several genes eg mutations in p53-> increased risk of cancer

94
Q

human papilloma virus increasing risk of cancer

p53

A

infection of cervix-> produces E6 protein which binds and inactivates p53. [Also produces E7 protein which binds and inactivates retinoblastoma gene product.] Increased risk of subsequent uncontrolled cell division-> precancer-> cancer

95
Q

What does normal p53 do and what happens if it becomes mutated or inactivated

A

Normally blocks cell cycle from progressing (at G1 and G2-M)
If mutated/inactivated the cell blocks become easier to bypass or not there at all —> uncontrolled cell division

p53 mutation leadign to loss of function important in numerous cancers

96
Q

c-myc

what is it, function/mechanism of action

A
  • transcription factor which binds lots of other genes
  • increases proteins which push cell towards cell division
  • increases other proteins which stop cell death (apoptosis)
  • overall effect= promote increased number of cells -proto-oncogene
97
Q

what happens when c-myc goes wrong

key flashcard

A
  • normal c-myc protein product tightly controlled
    When goes wrong:
  • breaks off with part of the chromosome to join another chromosome
  • at the join c-myc ends up beside the regulatory sequences of DNA for an immunoglobulin
  • if this happens in a B cell (which produces immunoglobulin) then get huge production of c-myc protein
  • pushes forward cell cycle and stops cells dying and promotes cancer
  • overexpressed c-myc is acting as an oncogene
  • c-myc often translocated from chromosome 8 to 14 in certain lymphomas
98
Q

translocation

A

when parts of chromosomes move and join other chromosomes, many cancers due to translocations of numerous genes

99
Q

environmental factors causing cancer

A

interact with the cell cycle genes and their products e.g. chemicals (smoking, alcohol), radiation (UV), infection (human papilloma virus), other= all increase risk of damage to DNA, environ agent acts on pre-existing normal gene or its protein product, causing it to be abnormal

100
Q

alochol increasing risk of cancer

A
  • Small amounts - completely metabolised in liver
  • Larger amounts - converted to acetylaldehyde (causes the red flushing of the face in some people) which then gets into systemic circulation-> causes double strand breaks of DNA in many genes-> increased risk of cancer
101
Q

inherited predisposition to cancer

A
  • Gene is already abnormal in cells (e.g. a pre-existing mutation)
  • It is not certain that cancer will occur but environmental mutations can then make it highly likely that cancer does occur
102
Q

Explain restinoblastoma as an inherited causes of carcinogenesis

A
  • A malignant tumour of the eye in children, runs in some families
  • autosomal dominant
  • in retinoblastoma the abnormal gene - the retinoblastoma gene - does not hold on to E2F molecules well
  • Sooo,cells enter S phase easily
  • 2nd environmental mutation in cell-> retina malignancy in childhood
103
Q

What is a good example of the multistep nature of carcinogenesis

A
  1. Epstein-Barr infection causing B cell proliferation and…
  2. c-myc being translocated and produced in large amounts

Both steps together lead to cancer (in particular one type of Burkitt lymphoma)

104
Q

What are central to cells dividing safely

A

Genes and their protein products (which relate to the cell cycle and repair of DNA damage, and chromosomes remaining intact)

105
Q

When do precancers and cancers arise

A

when genes, or their protein products are altered such that they gain or loose function

106
Q

What can alterations to genes/proteins (e.g. mutations) be from

A

environmental or inherited (or a mix of both)

107
Q

seminoma

A

malignant tumour of the testis

2. Foundations of Medicine PoD (28 decks)

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