Skin cancers 5

Question 1

Most common form of skin cancer?

Answer 1

BCC

Question 2

Where does BCC mainly occur?

Answer 2

Hair bearing skin–> mostly facial

Question 3

BCC tumour characteristics?

Answer 3

Highly invasive (destroy skin tissue)
Rarely metastasize

Question 4

BCC risk factors?

Answer 4

Significant cumulative ultraviolet light exposure
People more susceptible to sunburn (low pigmentation)
Immunosuppressed people.

Question 5

Genetic component of BCC?

Answer 5

Gorlins syndrome

Question 6

% of people with gorlins syndrome that develop BCC?

Answer 6

90

Question 7

BCC appearance?

Answer 7

open sores, red patches, pink growths, shiny bumps, scars or growths with slightly elevated, rolled edges and/or a central indentation

Question 8

BCC histology?

Answer 8

Tumour is connected to basal cell epidermis layer
Dermis is densely infiltrated with tumour cells
Palisade arrangement of nuclei

Question 9

Palisade arrangement meaning?

Answer 9

Parallel

Question 10

What is present in cSCC that is absent in BCC?

Answer 10

Keratin pearls

Question 11

Difference in nuclei between cSCC and BCC cells?

Answer 11

BCC cells have small nuclei

Question 12

What are the BCC tumour cells similar, morphologically, to?

Answer 12

Basal cells of the epidermis

Question 13

What % of sporadic BCCs have inactivating p53 mutations with a UV signature?

Answer 13

60-70%

Question 14

What pathway is mutated in 90% of the BCCs?

Answer 14

Hedgehog signalling pathway

Question 15

What receptor does SHH bind to?

Answer 15

Patched

Question 16

What happens once SHH binds to patched?

Answer 16

It is internalised and degraded in the lysosomes

Question 17

What does unbound Patched receptor do?

Answer 17

Inhibits smoothened

Question 18

Effect on smoothened of SHH binding to patched?

Answer 18

Smoothened becomes phosphorylated and moves to the membrane

Question 19

What does smoothened do at the membrane?

Answer 19

Recruits a protein complex

Question 20

What does the protein complex that smoothened recruits do?

Answer 20

Inhibits proteolysis, and results in transcription of hedgehog target genes

Question 21

What do hedgehog target genes do?

Answer 21

Increase proliferation and cell survival

Question 22

What happens in gorlins syndrome that can result in BCC?

Answer 22

Patched is mutated

Question 23

What cells do melanoma derive from?

Answer 23

Melanocytes

Question 24

Where do melanomas tend to develop?

Answer 24

In or near a mole

Question 25

Which groups are at greater risk of melanoma development?

Answer 25

Low pigmentation Prev sunburn People with many (more than 50) ordinary moles People who have already had one Immunosuppressed

Question 26

Early visual appearance of a melanoma?

Answer 26

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

Question 27

Development of melanoma appearance?

Answer 27

hard and lumpy, and bleed, ooze or crust up

Question 28

Typical histological feature of melanoma?

Answer 28

melanoma cells in upper layers of the epidermis, instead of melanocytes in basal layers of the epidermis

Question 29

Effect of melanoma on the dermis?

Answer 29

invasive tumor cells that have infiltrated into the dermis--> leads to abnormal melanin in the dermis

Question 30

What is dysplasia?

Answer 30

Abnormal development of cells within tissues

Question 31

What is the initiation of melanoma associated with?

Answer 31

activating mutations in the genes encoding for NRAS and BRAF.

Question 32

What does the N and B refer to in NRAS and BRAF?

Answer 32

Specific isoforms of RAS and RAF

Question 33

What does the mutations in the NRAS and BRAF genes cause in melanoma?

Answer 33

Constitutive pathway activation--> hyperactive MAPKinase signalling, and increase in cell growth and proliferation

Question 34

Which pathway are NRAS and BRAF components of?

Answer 34

MAPKinase pathway

Question 35

Why does the burst of proliferation stop in melanoma formation?

Answer 35

Oncogene induced senescence

Question 36

What follows the oncogene induced senescence in melanoma formation?

Answer 36

The naevus becomes dormant

Question 37

What can cause progression of a naevus to a melanoma in situ?

Answer 37

Several episodes of sunburn Cumulative sun exposure

Question 38

What genes cause UV induced progression to a melanoma in situ?

Answer 38

inactivating p53, pINC, P14ARF, P10

Question 39

What is p10?

Answer 39

An inhibitor of PI3Kinase signalling