Skin Cancer Flashcards
Define melanoma
A malignant tumor arising from melanocytes
What surfaces can melanoma arise from?
Mucosal (oral, conjunctival, vaginal)
Uveal tract of eye
Are pre existing nevi a risk for melanoma?
No
What is happening to the incidence of melanoma worldwide?
Its rising
What are the genetic risk factors for melanoma?
Family history
Lightly pigmented skin
Red hair
DNA repair defects
What are the environmental risk factors for melanoma?
Intense intermittent sun exposure Chronic sun exposure Residence in equatorial latitudes Sunbeds Immunosuppression
What are the phenotypic risk factors for melanoma?
> 100 Melanocytic nevi
Atypical melanocytic nevi
What role does the MAPK (RAS-RAF-MEK-ERK) pathway play in the pathogenesis of skin cancer?
It regulates cellular proliferation, growth and migration
What mutation is common in melanomas resulting from chronic sun exposure?
KIT
In what genes are active mutations present in in melanomas?
NRAS and BRAF genes
What do BRAF mutations lead to in the pathogenesis of melanomas?
Activation of the MPAK pathway
What is P-16?
A tumor supressor
What is P-16 encoded by?
CDKN2A
What does P-16 bind to?
CDK4/6
What is the effect of P-16?
It prevents the formation of cyclin D1-CDK 4/6 complex
What does cyclin D1-CDK 4/6 do?
Phosphorylates Rb, inactivating it, leading to E2F release (once released, E2F promotes cell cycle progression)
What role do CD8+ T cells play in melanoma?
They recognise melanoma-specific antigens and if activated appropriately, are able to kill tumour cells
What role do CD4+ T cells play in melanoma?
They play a critical role in the immune response against melanoma
How does CTLA-4 effect T cells?
It inhibits their activation by removing costimulatory signal
What might immunotherapy for melanoma be based on?
CTLA-4 blockade
Checkpoint inhibitors like PD-1, PDL1
What is the most common type of melanoma?
Superficial spreading melanoma
Where might superficial spreading melanoma arise?
De novo or in pre existing nevus (mole)
How do superficially spreading melanomas grow?
Slow horizontal growth phase
Rapid vertically oriented growth phase
