Melanin pigments and melanosomal proteins as differentiation markers unique to normal and neoplastic melanocytes

Abstract

This report introduces some aspects of our current basic research focus on the unique metabolic pathways within the melanocyte. Using this approach, we hope to gain a better understanding of the pathophysiology of malignant melanoma and develop early laboratory diagnostic tests for this disease. Specifically, we will discuss that: 1) the synthesis of pheomelanin is markedly increased in malignant melanoma and dysplastic melanocytic nevi; 2) high levels of metabolites of pheomelanin and eumelanin can be detected in the urine and blood of patients with metastatic melanoma; 3) this release of melanin metabolites appears to correlate with tumor thickness and tumor load, including the extent of metastasis; 4) the synthesis of melanosomal proteins also becomes aberrant in malignant melanoma; and 5) this abnormal melanosome synthesis can be utilized in the identification of antigenic epitopes that are uniquely expressed in malignant melanoma. We believe that this synthesis and secretion of abnormal melanin pigment and melanosomal proteins (human melanosome-specific antigen) would be useful for the development of early laboratory diagnostic and monitoring tools for malignant melanoma. In addition, we also report the detection of pheomelanin component in "normal" unexposed skin; however, the relative amount of pheomelanin in the skin does not reflect hair color (e.g., red hair). The nature of this pheomelanin component in the skin needs to be further clarified.