Tumour Pathology Flashcards
(107 cards)
1
Q
Ecotoderm
A
1 of 3 layers formed during embrionic development. Outermost: skin, neurons, mekanocytes
2
Q
mesoderm
A
1 of 3 layers formed during embrionic development. Middle: muscle, blood, bone, cartilage, endothelium, serous membranes
3
Q
Endoderm
A
1 of 3 layer formed during embrionic development. Innermost: lining of ariways, lining of gut, glands
4
Q
mucosa
A
combination of epithelium and CT
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
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
7
Q
Atrophy
A
Dec in number and/or size leading to dec organ size - pathological or physiological
8
Q
Metaplasia
A
Complete transformation of one differentiated tissue/cell type into a different differentiated cell/tissue type
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)
10
Q
neoplasia
A
An abnormal growth of tissue due to uncoordinated proliferation, it persists even after cessation of the stumuli
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)
12
Q
Cancer
A
A non-specific, non-technical term for a malignant neoplasm
13
Q
benign tumours in the epithelium (names)
2
A
adenoma, papilloma
14
Q
carcinoma
A
a malignant tumor that occurs in epithelial tissue e.g. adenocarinoma, squamous cell carcinoma
15
Q
sarcoma
A
malignant tumor of connective tissue e.g. leiomyosarcoma, osteosarcoma, liposarcoma, fibrosarcoma
16
Q
leukaemia
A
cancer of white blood cells e.g. acute myeoloid leukaemia, acute lymphoblastic leukaemia
17
Q
Lymphoma
A
malignant tumor of lymph nodes and lymph tissue/ lymphoid cells e.g. hodgkin’s lymphoma
18
Q
malignant tumour
A
cancerous, fast-growing, spreads easily
19
Q
what are not all “oma”???
A
neoplasia (granuloma is inflammatory)
20
Q
Summary venn diagram
A
see sheet ;)
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
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
23
Q
benign neoplasm of bone
A
osteoma
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
25
physical properties of cancer cells
* **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
26
How does the behaviour of cancer cells compare to that of normal cells
**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
27
10 steps
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
28
carcinogenesis
| features? and definition
* Tumour angiongenesis
* Apoptosis
* Necrosis
* Proto-oncogene, oncogene, tumour suppressor
Initiation of cancer formation
29
Tumour angiogenesis
The proliferation of a **network of blood vessels** which supplies a tumor with a s**upportive microenvironment rich with oxygen and nutrients** to **sustain optimal growth**.
Also an escape route...
30
Apoptosis
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
31
Necrosis
* **Premature (unregulated) cell death**
* A **passive** process
* **Toxic** cell contents leaked into extracellualr compartments
32
Define/explain:
* Proto-oncogene
* Oncogen
* Tumour suppressor
* 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
33
Explain/summarise the spread of cancer (**metastasis**)
* 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**
34
How do cancers spread (metastasis)?
| 4
* Local spread (tissue next to cancer)
* Lymphatic spread
* Haematogenous spread
* Trans-coelomic spread (within organ cavity)
35
Metastasis: lymphatic spread
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)
36
Metastasis: trans-coelomic spread
* 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)
37
potential sites of metastasis
| not sure if need to know
liver, lung, brain, bone, adrenal gland, omentum/peritoneum
38
What is it important to remeber about cancer occuring in certain sites
primary sites often always travel to same secondary site:
e.g. liver (from colorectal), bone (from breast, prostate), omentum/periotoneum (from ovary)
39
Vascular invasion
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**
40
local effects of benign tumours
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)
41
local effects of malignant tumours
* 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
42
local effects of tumours in different body parts
| (more general knowledge)
* 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
43
direct/local effects of cancer
| Learn - LO
* pain
* Loss of function
* haemorrhage
44
distant/systemic effects of cancer
| Learn -LO
* Deep Vein Thrombosis
* paraneoplastic syndrome
* cachexia (unexplained weightloss)
45
cachexia
| (systemic effect of cancer)
* weakness/**wasting due to chronic illness**
* can't necessarily be **fixed** by increasing nutrition
* usually **muscle loss > fat loss**
46
paraneoplastic syndrome
| (systemic effect of cancer)
* 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
How can we cure some cancer types before the cancer becomes established
by detecting precancer lesions
48
Dysplasia
* **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
Histology of dysplasia
* may be variation in nuclear size/shape
* increased mitotic activity
* abnormal mitotic forms
* cells often appears immature and irregular down the microscope
50
term for pre-cancer
dysplasia
51
Do all dysplasia form cancers
No, not all will become malignant
52
What can benign cancers cause
| overview of them (not specifics)
Symptoms, pain, death
53
What does the cervical screening programme look for
pre-cancer (cervical dysplasia) almost always cause by HPV virus
54
intraepithelial neoplasia
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
Briefly summarise process of ligand binding
| (signal transduction)
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
Give an example of a signal transduction molecule
BRAF
57
What does a T or arrow mean with regards to signal transduction
T = downstream molecule **inhibited**
Arrow = downstream molecule **activated**
58
How is activation/inhibition of a target molecule usually achieved
* Changing molecule shape
OR
* Adding another molecule (e.g. a phosphate group)
59
What are signalling molecules that go to the nucleus called
Transcription factors
60
transcription factors - function/signalling pathway
* 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
Quickly summarise the cell cycle
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**
6. M phases- mitotic phase where cellular division occurs
62
growth factor molecules
-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
G1 restriction point
| how can you progress, what does it act as?
* 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
Phosphorylation - how does it work to allow continuation through the cell cycle
| of protein at G1 restriction point
* 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
cell progression at G1 restriction point
| features
* 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
what is the protein "switch" that controls the restriction point called
Restinoblastoma gene product (Rb)
67
Restinoblastoma gene product (Rb)
* 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
What do growth factor molecules set off
pathway which ends up with phosphorylation of Rb gene product
69
What does Rb act as in its normal unphosphorylated (active) form
**tumour suppressor gene** as it **blocks** progression of cell cycle from going ahead
70
what inputs other than growth factors (promotors) are required for G1 progression
| phosphorylation of Rb gene promotors
Glucose levels, AA/growth factor levels both **high**
| lots of nutrients and growth factors
71
what is required to inhibit progression past G1 other than a lack of growth factors
| phosphorylation of Rb gene inhibitors
Lack of nutrients (e.g. glucose)
| although, lack of either would inhibit
72
What affects phosphorylation of the retinoblastoma gene product
multiple inputs; progression only happens when there are lots of nutrients and growth factors
73
HER-2
| inactive growth factors - function/what happens
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
what happens when there is damage to DNA?
| what molecule is activated and what does it do
-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
general/normal function of p53
stop cells dividing when they have damage to DNA
76
how is DNA damage repaired?
-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
function of proto-oncogene
to promote the cell to go through the cell cycle e.g. **growth factor**
78
how does an oncogene go wrong in cancer?
| examples
* 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
Tumour-suppressor gene definition/function
gene that regulates cell division - tend to control/block proto-oncogenes
80
One way an oncogene could cause cancer
when a growth factor receptor protein has a mutation that means it is overexpressed
81
How can tumour suppressor genes cause cancer
* Cause cancer when have **mutations**/environmental factors that **inactivate** them
* mutation can cause them to loose their function ---> cancer
82
how does a tumour-suppressor gene go wrong in cancer?
* Mutations - that s**top 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
Inherited causes of carcinogenesis
* 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
environmental causes of carcinogenesis
* 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
multistep nature of carcinogenesis
* 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
what can go wrong with HER-2 in breast cancer
* 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
BRAF
signal transduction molecule, proto-oncogene
88
what can go wrong with BRAF in malignant melanoma
| (skin cancer)
-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
What can cause the BRAF mutation
can be hereditary or environmental (e.g. sunlight damaging skin)
90
what can go wrong with the Rb gene product in Rb
* 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
how can MLH1 go wrong in colon cancer
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
smoking increasing risk of cancer
| p53
numerous chemicals in cigarette smoke-> metabolised to carcinogens in liver-> released into circulation-> damage DNA-> numerous mutations eg mutations in p53
93
radiation increasing risk of cancer
| p53
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
human papilloma virus increasing risk of cancer
| p53
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
What does normal p53 do and what happens if it becomes mutated or inactivated
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
c-myc
| what is it, function/mechanism of action
* 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
what happens when c-myc goes wrong
| key flashcard
* 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
translocation
when parts of chromosomes **move and join** other chromosomes, many cancers due to **translocations of numerous genes**
99
environmental factors causing cancer
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
alochol increasing risk of cancer
* 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
inherited predisposition to cancer
* 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
Explain restinoblastoma as an inherited causes of carcinogenesis
* 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
What is a good example of the multistep nature of carcinogenesis
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
What are central to cells dividing safely
**Genes and their protein products** (which relate to the cell cycle and repair of DNA damage, and chromosomes remaining intact)
105
When do precancers and cancers arise
when genes, or their protein products are **altered such that they gain or loose function**
106
What can alterations to genes/proteins (e.g. mutations) be from
environmental or inherited (or a mix of both)
107
seminoma
malignant tumour of the testis
