Melanoma biomarkers: current status and utility in diagnosis, prognosis, and response to therapy.

Melanoma is the most devastating form of skin cancer and represents a leading cause of cancer death, particularly in young adults. As even relatively small melanomas can readily metastasize, accurate staging of progression is critical. Diagnosis is typically made on the basis of histopathologic criteria; with tumor thickness (Breslow), invasion level (Clark), ulceration, and the extent of lymph node involvement being important prognostic indicators. However, histologic criteria alone cannot diagnose all melanomas and there are often problems in distinguishing subsets of benign nevi from melanoma. There also exists a group of patients with thin primary melanomas for whom surgery should be curative but who ultimately go on to develop metastases. Therefore, there is an urgent need to develop molecular biomarkers that identify melanoma patients with high-risk primary lesions to facilitate greater surveillance and possible adjuvant therapy. The advent of large-scale genomic profiling of melanoma is revealing considerable heterogeneity, suggesting that melanomas could be subgrouped according to their patterns of oncogenic mutation and gene expression. It is hoped that this subgrouping will allow for the personalization of melanoma therapy using novel molecularly targeted agents. Much effort is now geared toward defining the genetic markers that may predict response to targeted therapy agents as well as identifying pharmacodynamic markers of therapy response. In this review, we discuss the utility of melanoma biomarkers for diagnosis and prognosis and suggest how novel molecular signatures can help guide both melanoma diagnosis and therapy selection.