Integrity: Cancer Pathology Flashcards
Definitiion of atrophy
- Atrophy
- Shrunken tissue with reduced cell size (± number)
Definition of hypertrophy
Hypertrophy
* Enlargement of a tissue with increased cell size
Definition of hyperplasia
Hyperplasia
* Increased number of otherwise normal cells in a tissue
Definition of transdifferentiation
Transdifferentiation
* A switch of differentiation direct from one mature lineage to
another which is normally present in that tissue
Definition of metaplasia
Metaplasia
* A switch of differentiation from one mature phenotype to
another which is not normally present in that tissue,
in response to an environmental change.
Definition of dysplasia
Dysplasia
* Disordered microscopic appearance and maturation of cells,
implying neoplasia.
Definition of a tumour
Tumour
* Abnormal lump of no specific cause (often presumptively a neoplasm)
Definition of a cyst
Cyst
* Abnormal fluid-filled lesion lined with epithelium
Definition of a hamartoma
Hamartoma
* Disorganised but mature normal tissue elements, lacking autonomous growth
Definition of neoplasm
Neoplasm
* Abnormal accumulation of cells derived from a mutated ancestor ‘seed’ cell
* growth is autonomous of environmental restraining signals
Deinition of cancer
Cancer = a malignant neoplasm
- Invasion: crosses tissue boundaries
- Metastasis: discontinuous spread to survive & grow at remote sites
- carriage in: blood / lymph / serous cavity fluid / CSF (cerebrospinal fluid)
How is the craniospinal venous system relevent in metastasis?
- 2-way venous flow (no valves)
- Links cranial + vertebral circulation
with intercostal, abdominal & pelvic
venous plexuses - Direct ’back-door’ route for metastasis
to spine and brain - skips lungs, lymphatics
- e.g. from prostate, breast, thyroid.
6 appearances of surface neoplasms
Definition of carcinoma
Carcinoma is cancer that forms in epithelial tissue
What is a sarcoma?
Sarcoma is the general term for a broad group of cancers that begin in the bones and in the soft (also called connective) tissues (soft tissue sarcoma)
What is Cachexia
progressive muscle dysfunction + lean muscle wasting (+/- adipose loss), not reversible with nutritional support
What is paraneoplastic?
Paraneoplastic = a problem caused by a neoplasm but not attributable to cancer invasion or secretion of indigenous tissue hormone aka it’s directly, physically or anatomically affecting an organ
What is clonal expansion?
This is a normal process where you aquire cancer driving mutations (onces that encourage growth) but they don’t progress further, if these fill a neish well they will expand and outcompete the surrounding cells
What happens with clonal expansion and age?
Clonal expansion increases with age and to varying degrees in different sites
What is a cancerisation field?
Cancerisation field
A tissue with accumulated genetic & epigenetic changes that favour
cancer emergence
Field cancerisation:
Mutation count & clonal patch sizes increase with…
Mutation count & clonal patch sizes increase with
- chronic inflammation (cycles of destruction and regeneration)
- carcinogens: sun exposure, smoking, alcohol
Consequence of non-cancerous clonal haematopoiesis
clonal haematopoiesis is pro-inflammatory
* Coronary heart disease & stroke (larger risk than hypertension)
What has the highest risk of tissue that is
Normal
Hyperplastic
Metaplastic
Dysplastic
Dysplastic
Usually means it has gotten much bigger
How does cancer arise from clonal expansion: clonal sweep
What are the hydrodynamics of a tumour and why is it relevent?
The core has a very high interstitial (between cells) pressure resulting in an area with poor diffusion, hypoxia, acidic and ripe for ischemia.
This hypoxia produces a strong selection bias for angiogenesis in growing cancers (through HIF - hypoxia driven gene expression and angiogenic factors)
The flow of fluid is also radially outward from the core and then towards the lymphatic drains.
This makes it hard for drugs to diffuse into the core and promotes cells migration towards the lymphatics
Key points:
* High core pressure
* Hypoxia in core which promotes angiogenesis selection bias
* Prevents drugs from reaching core and promotes spread outward towards lymphatics
WHat is angiogenesis?
The creation of new blood vessels
What’s happening here?
Competition for blood in cancer creates dissorganised angiogenesis
This results in non-hierarchical unstable haemodynamics
- pooling, eddies, flow reversals
- pO2 varies in “waves & tides”
What is a cancer driver gene?
Most human cancers have 2-8 mutant drivers
> 500 total but most early cancers have mutations in the same 9 genes
Typically they affect multiple cancer hallmarks, suppressing some and promoting others
How are do key drivers differ after treatment?
Key driver mutations are often ubiquitous in untreated cancer + its metastases
- New mutations often have no selective impact: neutral passenger mutations in ‘subclones’
After treatment you are applying new pressures which unmask previously neutral or minority but resistant subclones
Key cancer mutation hallmarks
4 Early
4 Late
Early
- Promotes proliferation genes
- Surpresses anti-proliferation genes
- Unlimited copying - removes caps that normal cells have whereby they can only be copies so many times before the quality becomes worse
- Metabolic reprogramming for energy
Late
- Evasion of immune system
- Resisting aopoptitic mechanisms
- Invasion and metastasis
- Angiogenesis
What do we mean by plasticity when it comes to cancer cells
Many have an ability to change state, whether this is a speciality state or a stem state.
This means they can often adapt to differing pressures
What does epithelial-mesenchymal plasticity (EMP) mean?
Some cancer cells can switch between being epithelial and mesenchymal
Why is relapse quite common?
Risidual cells are often left behind after treatment (these can be a handful of subclones)
These are then treatment resistant and spread making a second treatment less successful
What is Replicative Senescence and what is used to overcome replicative senescence in germ and stem cells
Replicative senescence is the phenomenom where cells can only divide so many times.
The end of chromosomes are clipped with repetitive sequences called telomeres. These shorten with every division eventually resulting in apoptosis.
Telomerase is present in stem cells and germ cells in order to maintain telomere ends which results in unlimited replication.
Telomerase is abnormally upregulated in cancer cells
What are the loops on the ends of chromosome designed to cap unlimited cell replication called?
Telomeres
What substance can maintain telomeres during replication?
Telomerase
What is Retinoblastoma?
Retinoblastoma is a rare childhood cancer of retinoblasts, with a peak
incidence at 3-4 years of age
What is the difference between an inherited retinoblastoma and a sporadic one?
You need a loss of both RB1 genes.
In the inherited version one is lost in every cell already hence if the other spontaineously mutates in any cell it results in the retinoblastoma. Bilateral likely.
In spontaineous if one cell mutates loss of one RB1 gene then the mutation would have ot happen in the same cell therefore it would likely only be in one eye. Unilateral.
Syndromes in which the heterozygotes express the tumour phenotype
(one mutation inherited form one parent however there will be one unmutated allele)
Syndromes in which the homozygotes
have an increased risk of cancer
(you need to inherit two of the same in order to have an increased risk of cancer?)
In terms of oncogene activation, what is a point mutation?
This is where the mutation occurs by one part of a codon switching
In terms of oncogene activation, what is amplification
This is where one gene get copied over and over thus amplifying it’s effect
In terms of oncogene activation, what is innapropriate regulation
This is where a promotor is present where it shouldn’t be thus activating a gene where it shouldn’t be activated
Are oncogenes considered dominant or recessive?
Oncogenes activate tumour promoting factors therefor if one is switched on it has an effect hence they are considered dominant
Are tumour suppressor genes considered dominant or recessive?
With a tumour suppressor genes these are genes whic work to surpress tumour function. You only need one to function in order to suppress the tumour hence both need to mutate in order for suppression to fail so they are considered recessive
What is p53 protein?
This is a protein which is released in response to DNA damage which arrests the cell and stops it proliferating.
The p53 gene is therefore a tumour suppressing gene
How does damage to exision repair encourage cancer?
DNA repair by exision of mutation is key to maining DNA. If this is inhibited mutation are more likely to stick
How does damage to DNA strand break repair cause cancer?
BRCA1 & BRCA2 involved in d/s break repair. If the genes producing BRCA1 & BRCA2 are mutated then DNA is less likely to able to repair itself
