Molecular testing in cutaneous melanoma

Cutaneous melanoma is associated with strong prognostic phenotypic features such as gender, Breslow's thickness, and ulceration although the biological significance of these variables is largely unknown. It is likely that these features are surrogates of important biological events rather than promoting directly melanoma progression. High-throughput expression studies have helped deciphering the mechanism and role of melanoma cells replication. Another important phenotypic variable in melanoma is the presence of histopathological features of chronic sun exposure damage. The presence or absence of solar elastosis correlates with the rate and the type of BRAF mutations. Genetic defects found in cutaneous melanoma involve most often receptor tyrosine kinase and downstream kinase pathways. Thus, the mitogen-activated protein kinase pathway and the PI3K pathway are activated in most melanomas. BRAF has a recurrent gain-of-function mutation V600E in about 7 % of all cancers and 43-50 % of melanomas. Anti-BRAF therapy has been the first targeted therapy of metastatic melanomas and completely changed the therapeutic landscape. One of the most important unmet needs in the melanoma field is to shift from prognostication based on artificial segmentation of continuous variables to continuous likelihood scores for diagnosis, prognosis, and response to treatment predictions. This implies to use shared biomarkers and clinical databases.