Session 5 - Melanoma Flashcards

Question

Outline the ABCDE criteria for assesing moles

Answer 1

 A = asymmetry  B = border is irregular  C = colour is variable (black/brown/red/white)  D = diameter > 6 mm (approximately the size of the blunt end of a pencil) - E = Evolving

Answer 2

Major features: change in size, shape or colour. |  Minor features: inflammation, bleeding or crusting, sensory change and a lesion of 7 mm or greater.

Answer 3

Any one major feature or two minor features would merit consideration for excision.

Answer 4

Mutation of the NRAS/BRAF (protein kinase) gene, which forms part of the MAPK pathway involved in cell signallling. NRAS OR BRAF mutation -> MAPK pathway permanently ON -> Cell cycle entry -> Proliferation

Answer 5

Mutation in CDKN2A tumour supressor gene, which prevents production of p16INK4A (cyclin dependent kinase inhibitor which supresses cell progression) and p14ARF (similar mech, but via p53).

Answer 6

CDKN2A increases p53 activity via P14ARF, which can induce apoptosis. Mutation and loss of CDKN2A means this pathway not available. Activation of AKT signalling also important in evasion of apoptosis (AKT is path which supresses apoptosis). AKT sig activated by MAP kinase path - inappropriate activation of path OR deleation of PTEN gene (AKT supressor) activates this path.

Answer 7

Rapid growth -> Hypoxia -> HIF (hypoxia inducible factor) -> VEGF expression

Answer 8

Increased growth | Increased chance of metastases.

Answer 9

1.Invasion - detachment of either small groups or individual cells from the main tumour mass; these cells must then travel through adjacent tissues. 2. Transport to distant sites by entering blood vessels, lymphatic vessels or body cavities. 3. Thriving in a new site - cancer cells must escape from blood or lymphatic vessels (this is called extravasation) or, if they invaded a body cavity, grow within it at a distant site or escape into surrounding distant tissues, where they form a secondary tumour. 4. Escape immune destruction at each step

Answer 10

``` Changes in cell adhesion molecules as cells break away from the main tumour mass, such as switching from a type of cadherin called E-cadherin, which promotes binding of melanoma cells to each other, to a different type of cadherin called N cadherin, which mediates binding between melanocytes and fibroblasts. This switch in cadherin class enables melanoma cells to detach from each other and to interact with fibroblasts as they invade into the stroma. ``` many different types of matrix metalloproteinase enzymes have been found to be altered in melanoma

Answer 11

melanocytes that lack key cyclin dependant kinase inhibitors such as p21 (induced by p53) and p16, the cells proliferate until they reach what is called crisis. In crisis, the telomeres have become eroded because the absence of cyclin-dependant kinases means that relicative senescence cannot occur. There is therefore massive cell death due to chromosomal fusions. However, a tiny number of cell clones emerge and these have become immortal. This is achieved by re-activation of the enzyme telomerase, which is capable of synthesizing new telomeres. Telomerase has a catalytic part called hTERT and an RNA part that primes synthesis of new telomeres. It is hTERT that becomes expressed. Once the telomeres can be maintained, indefinite proliferation is possible.

Answer 12

- accurate diagnosis - Understanding of tumour natural history, and thus prognosis - What therapeutic agents it will respond to

Answer 13

“How to make a melanoma: what do we know of the primary clonal events?” Pigment Cell Melanoma Res. 2008;21(1):27-38.