Skin cancers 5 Flashcards
Most common form of skin cancer?
BCC
Where does BCC mainly occur?
Hair bearing skin–> mostly facial
BCC tumour characteristics?
Highly invasive (destroy skin tissue)
Rarely metastasize
BCC risk factors?
Significant cumulative ultraviolet light exposure
People more susceptible to sunburn (low pigmentation)
Immunosuppressed people.
Genetic component of BCC?
Gorlins syndrome
% of people with gorlins syndrome that develop BCC?
90
BCC appearance?
open sores, red patches, pink growths, shiny bumps, scars or growths with slightly elevated, rolled edges and/or a central indentation
BCC histology?
Tumour is connected to basal cell epidermis layer
Dermis is densely infiltrated with tumour cells
Palisade arrangement of nuclei
Palisade arrangement meaning?
Parallel
What is present in cSCC that is absent in BCC?
Keratin pearls
Difference in nuclei between cSCC and BCC cells?
BCC cells have small nuclei
What are the BCC tumour cells similar, morphologically, to?
Basal cells of the epidermis
What % of sporadic BCCs have inactivating p53 mutations with a UV signature?
60-70%
What pathway is mutated in 90% of the BCCs?
Hedgehog signalling pathway
What receptor does SHH bind to?
Patched
What happens once SHH binds to patched?
It is internalised and degraded in the lysosomes
What does unbound Patched receptor do?
Inhibits smoothened
Effect on smoothened of SHH binding to patched?
Smoothened becomes phosphorylated and moves to the membrane
What does smoothened do at the membrane?
Recruits a protein complex
What does the protein complex that smoothened recruits do?
Inhibits proteolysis, and results in transcription of hedgehog target genes
What do hedgehog target genes do?
Increase proliferation and cell survival
What happens in gorlins syndrome that can result in BCC?
Patched is mutated
What cells do melanoma derive from?
Melanocytes
Where do melanomas tend to develop?
In or near a mole
Which groups are at greater risk of melanoma development?
People more susceptible to sunburn
Past episodes of severe sunburn, often with blisters, and particularly in childhood.
People with many (more than 50) ordinary moles
People who have already had one
People with a damaged immune system
Visual appearance of a melanoma?
minor changes in the size, shape or colour of an existing mole; others begin as a dark area that can look like a new mole
Development of melanoma appearance?
hard and lumpy, and bleed, ooze or crust up
Typical histological feature of melanoma?
the presence of melanoma cells in the upper layers of the epidermis (as opposed to the localization of normal melanocytes in basal layers of the epidermis
Effect of melanoma on the dermis?
invasive tumor cells that have infiltrated into the dermis–> leads to abnormal melanin in the dermis
What is dysplasia?
Abnormal development of cells within tissues
What is the initiation of melanoma associated with?
activating mutations in the genes encoding for NRAS and BRAF.
What does the N and B refer to in NRAS and BRAF?
Specific isoforms of RAS and RAF
What does the mutations in the NRAS and BRAF genes cause in melanoma?
Constitutive pathway activation–> hyperactive MAPKinase signalling, and increase in cell growth and proliferation
Which pathway are NRAS and BRAF components of?
MAPKinase pathway
Why does the burst of proliferation stop in melanoma formation?
Oncogene induced senescence
What follows the oncogene induced senescence in melanoma formation?
The naevus becomes dormant
What can cause progression of a naevus to a melanoma in situ?
Several episodes of sunburn
Cumulative sun exposure
What genes cause UV induced progression to a melanoma in situ?
inactivating p53, pINC, P14ARF, P10
What is p10?
An inhibitor of PI3Kinase signalling
