Melanoma has a reputation as an unpredictable disease, but investigation has demonstrated a multiplicity of factors which are independently associated with melanoma incidence and prognosis. Major factors associated with melanoma incidence include those related to race and ethnicity, sunlight exposure, and genetic and familial predisposition. Major factors associated with melanoma prognosis include tumor thickness, ulceration, anatomic location, and patient's sex. These factors are clinically important in designing appropriate screening and prevention programs, as well as in selecting appropriate treatment and follow-up for the individual melanoma patient.
There is an increasing need to identify the molecular mechanisms underlying these clinically defined etiologic and prognostic factors so that we may treat patients more effectively and more selectively. Available evidence indicates that the mechanisms of melanoma etiology include a loss of tumor suppressor genes. Mechanisms of melanoma progression include the accumulation of oncogene mutations, perhaps as a result of sun exposure, the development of autocrine and paracrine loops involving cytokines and growth factors, and alterations in cell-surface antigen expression. Finally, an antigen-specific immune response to melanoma appears to be important in the prognosis of some patients. Critical regulatory components of the melanoma immune response include antibodies, T-cells, and human leukocyte antigen (HLA) molecules.