Cancer 14: Skin Cancer

What are the three most common skin cancers?

1.) Basal cell carcinoma 2.) Squamous cell carcinoma 3.) Melanoma

Melanin is packed into melanosomes and transferred to keratinocytes via dendritic processes which are then phagocytosed. What are the two different types of melanin formed?

1.) Eumelanin - brown/black 2.) Phaeomelanin - yellowish or reddish brown

What are the four clinical subtypes of melanoma?

1.) Superficial spreading melanoma 2.) Nodular 3.) Lentigo maligna 4.) Acrolentiginous

Radiotherapy in childhood increases the risk of developing melanoma by...

13 times

p53 is found on the short arm of chromosome...

17

Squamous cell carcinomas are tumours of the elderly that develop from...

Basal keratinocytes

How are the aforementioned DNA defects removed?

Base excision repair (DNA replication is arrested, the dimer is excised and repair is accomplished using ligase and polymerase

What is the genetic defect in xeroderma pigmentosum? What type of genetic condition is it?

Defect in nucleotide excision repair. Autosomal or sex-linked recessive

What forms an epidermal melanin unit?

One melanocyte associated with 36 keratinocytes

Which of these types of melanin is soluble in alkali?

Phaeomelanin. Eumelanin is insoluble

From where do basal cell carcinomas arise?

Pluripotent stem cells in the epidermis

In what bodily areas are basal cell carcinomas most common?

Sun-exposed e.g. face, ears, neck, back, chest and legs

Langerhans cells are distributed in which cellular later?

Suprabasilar epidermal layer

What promotes the switch from phaemelanocortin to eumelanin

The melanocortin 1 receptor

What is meant by the Sun Protection Factor?

Time taken in the sun with a sunblock before the skin redness develops 24 hours later divided by the time taken in the sun without sunblock before redness develops 24 hours later

True or false: 100x more UVA than UVB penetrates the earth's surface and is the major cause of skin ageing

True

True or false: UVA can also form cyclobutane butane pyrimidine dimers

True

True or false: basal cell carcinomas are locally destructive but not generally metastatic

True

True or false: melanin is formed from tyrosine via a series of enzymes

True

True or false: melanin is the pigment responsible for skin colour

True

True or false: melanoma is associated with intermittent intense sun exposure and sunburn before 15 years

True

True or false: p53 binds to DNA as a tetramer

True

True or false: squamous cell carcinoma may arise from precursor lesions including Bowen's disease and solar keratoses

True

True or false: the melanocortin 1 receptor regulates skin and hair pigmentation phenotype

True

True or false: presence of dysplastic naevae is a risk factor for developing melanoma

True - these are abnormal moles. Other risk factors include family history, higher SES, arsenic exposure in farmers, airline pilots and use of tanning beds for more than 1 month

True or false: apoptosis is one defence mechanism against UV damage

True. The is mediated by action of Bax transcription which heterodimerises antioxident Bcl-2 associated with mitochondrial membrane

True or false: the density of Langerhans cells decreases following UV exposure

True. This is because they are also sensitive to UV damage

True or false: tanning is a method of cutaneous protection against UV exposure

True. This occurs due to redistribution and alteration of melanin

True or false: mutation in one p53 allele can inactivate wild type p53

True. This results in failure of p53 to arrest cell division => division of cells with daughter cells acquiring damaged DNA

What is the single most important factor in the pathogenesis of skin cancer?

UV light exposure - so sunlight exposure

How else may UVA light damage DNA?

UVA exposure results in the formation of singlet oxygen and free radicals. Characteristically results in T -> G conversions

Which subtype of UV light is most important in skin carcinogenesis?

UVB

How does UVB directly induce abnormalities in DNA?

UVB induces formation of cyclobutane butane pyrimidine dimers e.g. thymine dimers are most commonly detected in 85% of UV-irradiated DNA. They also induce formation of 6-4 pyramidine-pyramidone photoproducts

Is this lecture soul-destroying or what?

Yes, yes it is.

How do elevated levels of p53 mediate growth arrest in G1?

p53 induces transcription of p21, which inhibits proliferating cell nuclear antigen PCNA. This inhibits activation of Cdks and thus cell cycle regulating cyclins.

What kind of genetic disorder is basal cell naevus syndrome?

Autosomal dominant

What is the relationship between the wavelength and carcinogenic potential of a wave?

Carcinogenic potential is proportional to the reciprocal of the wavelength i.e. smaller wavelength, higher carcinogenic potential

What produces melanin?

Epidermal melanocytes in the basal layer of the epidermis

True or false: basal cell carcinomas are usually cancers of the young

False - they are cancers of the elderly

True or false: 6-4 pyramidine-pyramidone photoproducts are less mutagenic but more slowly repaired than cyclobutane butane pyramidine dimers

False. 6-4 pyramidine-pyramidone photoproducts are MORE mutagenic but repaired 1.5x faster.

True or false: different skin colour is dependent on melanin density

False. Melanin density is fairly constant; what differs is the amount and type of melanin

True or false: squamous cell cancers are not metastatic

False. They are metastatic, spreading to regional lymph nodes and then solid organs, particularly the lung

True or false: all subtypes of UV light penetrate the stratosphere

False. UVC is stopped by the stratosphere, whereas UVA and UVB penetrate

True or false: melanoma usually occurs in sun-exposed areas

False. Usually occurs in non-exposed areas.

How are Langerhans cells involved in cell-mediated toxicity?

Langerhans cells have complex dendritic processes which cover 25% of the skin surface. They recognise tumour-associated antigens which they then process and present to T cells

What age range is mainly affected in melanoma and from what type of cell does it develop?

Mainly affects young people (but can occur at any age) and develops from epidermal melanocytes or rarely dermal melanocytes.

Melanin is a chromophore for UV light. What does this mean?

Melanin absorbs UV light and thyus provides protection for most sensitive levels of the lower skin. Melanin also traps electrons and free radicals

What are melanocortins?

Melanocortins are peptides derived from propiomelanocortin precursor proteins comprising ACTH, MSH, lipotrophins and endorphins

What can be said about the metastatic potential of melanoma?

Melanoma is highly metastatic, spreading to regional lymph nodes and then solid organs, especially the lungs, liver and brain