Cancer as a disease - Skin cancer Flashcards
What are the five layers of the epidermis? (superficial to deep)
Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale
Then have a basement membrane to separate the underlying dermis
What are the main cell types in the epidermis?
Keratinocytes
Melanocytes
Langerhans Cells (dendritic)
Merkel Cells
State the types of skin cancer that come under each of the following types:
a. Keratinocyte derived
b. Melanocyte derived
c. Vasculature derived
d. Lymphocyte derived
a. Keratinocyte derived Basal Cell Carcinoma Squamous Cell Carcinoma b. Melanocyte derived Malignant Melanoma c. Vasculature derived Kaposi Sarcoma – endothelium of lymphatics Angiosarcoma – endothelium of blood vessels d. Lymphocyte derived Mycosis fungoides
State two examples of genetic syndromes that massively increase the risk of getting skin cancer. Which ones?
Gorlin’s Syndrome – regular BCCs
Xeroderma Pigmentosum – increased risk of BCC, SCC and malignant melanoma
Give two examples of viruses that can lead to skin cancer?
HHV8 in Kaposi’s sarcoma
HPV in SCC
State two other known causes of skin cancer
UV light => BCC, SCC, MM
Immunosuppression
What is the difference between the depth reached by UVB radiation and UVA radiation?
UVB – reaches sea level
UVA – reaches dead sea level
What is the most important wavelength category of UV in skin carcinogenesis?
UVB
note that UVA also contributes to skin carcinogenesis
Which wavelength category of UV is the major cause of skin ageing?
UVA
How is UVA radiation used therapeutically?
used therapeutically in PUVA therapy (psoralen and ultraviolet A)
How does UVB cause mutations in DNA?
UVB induces photoproducts, specifically pyrimidine dimers (normally repaired by nucleotide excision repair)
How can UVA promote skin carcinogenesis?
- Forms cyclobutane pyrimidine dimers (but less effectively than UVB)
- Generates free radicals that can damage DNA and cell membrane
Name a genetic condition with defective Nucleotide Excision Repair
Xeroderma pigmentosum
patients develop skin cancers at a very young age with minimal sun exposure
What are the features of XP?
Increased risk of BCCs, SCCs and melanoma
Photosensitivity and dry skin
What happens to keratinocytes in sunburn? What does this prevent?
The UV damage leads to keratinocyte apoptosis (the apoptotic cells are called ‘sunburn’ cells).
Apoptosis removes UV damaged cells in the skin which might otherwise become cancer cells.
Describe the immunomodulatory effects of UV light.
UVA and UVB affect the expression of genes involved in skin immunity
It depletes Langerhans cells in the epidermis
This reduces skin immunocompetence and immunosurveillance
How may the immunomodulatory effects of UV light be used therapeutically?
What are the potential negative consequences?
UV phototherapy for e.g. psoriasis
UV can act on keratinocytes and cause DNA damage; Langerhans cells have been depleted and so they will be unable to knock out the damaged cells, which could then persist and become cancerous
Which system is used to categorise people based on their skin type and hence sensitivity to UV?
Fitzpatrick Phenotypes
Which epidermal cell produces melanin? What layer of epidermis is it found in?
Hence state what skin colour depends on?
Produced by melanocytes within the basal layer (stratum basale) of the epidermis.
Skin colour depends on the amount and type of melanin produced not the density of melanocytes (which is fairly constant).
What happens to melanin once it is produced by the melanocytes?
How does UV exposure cause more melanin to be produced?
- It is packaged into melanosomes and it travels down the dendritic processes of the melanocytes and is taken up by the keratinocytes.
- The keratinocytes put the melanosomes around their nuclei, which protects the nuclei from DNA damage
- UV exposure causes the keratinocytes to release melanocyte stimulating hormone which will make adjacent melanocytes produce more melanin (paracrine signalling)
What are the two types of melanin? What are their colours?
Eumelanin – black/brown
Phaeomelanin – yellowish or reddish-brown
What is melanin formed from?
formed from tryosine via a series of enzymes
What gene encodes for the production of melanin?
Explain the variation in eumelanin:phaeomelanin produced.
MCR1 gene
> 20 gene polymorphisms of the gene explains the different hair colours and skin types
What is malignant melanoma? What is the major risk?
Malignant tumour of melanocytes; melanocytes become abnormal
