Potential tumor markers

Malignant melanocytes present defective melanosomes and tend to exhibit up-regulated melanogenesis. Melanogenuria (in the form of dark urine) is observed in some patients with widespread disease. End-product pigments, enzymes and melanin precursors or intermediates of the melanogenesis have therefore been measured in urine and blood from melanoma patients for more than 30 years.

Based on its key regulating role, the melanocyte-specific enzyme tyrosinase has been evaluated by the measurement of its activity (abandoned due to poor sensitivity), substrates and/or metabolites (L-tyrosine, l-DOPA) and, more recently, by the detection and now quantification of specific mRNAs, mostly in blood (plasma or serum). Tyrosinase appears to be the most reliable mRNA target for RT-PCR: it is a specific marker of melanocytic differentiation, expressed both in primary and metastatic melanoma. Many researchers aiming at the detection of melanoma cells in blood, bone marrow, lymph nodes and sentinel nodes have pursued this promising line of investigation. Unexpectedly, the results are so far extremely variable and sometimes negative in advanced melanoma patients.

Other evaluated serological markers from the melanogenesis pathway include the phaeomelanin metabolite 5-S-CD (see Ref. 5 for an review of 5-S-CD in melanoma with 2648 samples taken from 218 patients) and to a lesser extent the eumelanin metabolite 6-hydroxy-5-methoxyindole-2-carboxylic acid. Since 5-S-CD is very sensitive to light and oxidation, analysis requires immediate centrifugation, freezing of the samples after blood collection and exclusion of light and air-oxygen.

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