clinical oncology Flashcards
skin cancer: summarise the epidemiology of skin cancer, define basal cell carcinoma, squamous cell carcinoma, melanoma and epidermodysplasia verruciformis; explain the role of UV light in the pathogenesis of skin cancer and the role of p53 in relation to this; summarise the role of human papilloma virus in the pathogenesis of squamous cell carcinoma
3 layers of skin (superficial to deep)
epidermis -> dermis -> hypodermis (contains subcutaneous fat and muscle)
structure of epidermis (from young at bottom, old at top)
dermis -> stratum basale -> stratum spinosum -> stratum granulosum -> stratum lucidum -> stratum corneum
what is present in dermis
sensory nerve ending
what is present in stratum basale
dividing keratinocyte (stem cell), tactile cell, melanocytes (sit on top of basement membrane)
what is present in stratum spinosum
dendritic cell, living keratinocytes
what is present in stratum corneum
dead keratinocytes (those on surface flake off)
examples of keratinocyte derived skin cancer (non-melanoma skin cancer - NMSC)
basal cell carcinoma, squamous cell carcinoma
example of melanocyte derived skin cancer
malignant melanoma
example of vasculature derived skin cancer (rarer)
Kaposi’s sarcoma (common in AIDS), angiosarcoma
example of lymphocyte derived skin cancer
mycosis fungoides
generic cause of skin cancer
accumulation of genetic mutations in key genes leading to uncontrolled cell proliferation
4 factors causing skin cancer
genetic syndromes (e.g. Gorlin’s causing basal cell carcinoma; xeroderma pigmentosum preventing DNA repair), viral infections (HHV8 causing Kaposi’s sarcoma; HPV causing squamous cell carcinoma), UV light (basal cell carcinoma, squamous cell carcinoma, malignant melanoma), immunosuppression (e.g. by drugs, HIV, old age, leukaemia)
UV spectrum from x-rays (low wavelength) to visible light (high wavelength)
UVC -> UVB -> UVA
perforation of UV spectrum
UVC to stratosphere, UVB to ground, UVA through water
4 effects of sunlight
photosynthesis, IR provides warmth, effect on human mood, stimulates vitamin D production in skin
what UV spectrum is most important wavelength in skin carcinogenesis
UVB
3 features of UVA concerning proportion, aging, skin carcinogenesis and PUVA therapy
100x more UVA penetrates surface than UVB, major cause of skin aging, contributes to skin carcinogenesis, used therapeutically in PUVA therapy for psoriasis
effect of UVB in DNA
induces photoproducts (mutations), causing cross-linking of pyrimidines (cytosine and thymine, causing e.g. thymine dimers)
what usually repairs UVB-induced photoproduct mutations
nucleotide excision repair
how does UVA promote skin carcinogenesis
DNA forms cyclobutane butane pyrimidine dimers (less efficiently than UVB), produces free radicals damage DNA and cell membrane
3 specific gene types involved in UV damage to DNA
cell division, DNA repair, cell cycle arrest
genetic condition with defective nucleotide excision repair (removes photoproducts)
xeroderma pigmentosum
presentation, diagnosis and treatment of xeroderma pigmentosum
before 10, extensive freckling, photosensitivity; genetic testing; remove skin cancers and strict sun protection
3 effects of mutations which cause cancer
stimulate uncontrolled cell proliferation (e.g. p53), alter responses to growth stimulating/repressing factors, inhibit apoptosis
what is sunburn and why
apoptotic ketatinocytes in UV overexposed skin (apoptosis removes UV damaged cells in skin which might otherwise become cancer cells)
describe 3 outcomes of photocarcinogenesis
UV -> DNA damage -> skin cancer / DNA repair / apoptosis of irrepairable DNA
what cells do UVA and UVB deplete in epidermis involved in skin immunity, and what they do
Langerhans cells (APCs which trigger immune response in malignant cell, causing cell death)
what is basis for UV phototherapy for e.g. psoriasis, and what is consequence of using phototherapy
reduced skin immunocompetence and immunosurveillance, however this further increases cancer causing potential of sun exposure
what determines host response to UV
genetic influences especially skin phototype