High Plasma Level of a Eumelanin Precursor, 6-Hydroxy-5-Methoxyindole-2-Carboxylic Acid as a Prognostic Marker for Malignant Melanoma

Abstract

Melanin synthesis is a biologic property unique to the melanocyte. It is highly elevated in malignant melanoma with the production of both eumelanin (brown/black pigment) and pheomelanin (yellow/red pigment), dihydroxyindole (DHI) and cysteinyldopa (CD), respectively, being major precursors. Melanin metabolites are often released in the urine of patients with disseminated melanoma metastasis (melanuria). To establish a better method for the detection of occult melanoma this study compares the plasma levels of a pheomelanin metabolite, 5-S-CD, and a eumelanin metabolite, 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C), in melanoma and non-melanoma patients and correlates them with tumor thickness and melanoma metastasis. We found a) that the normal plasma levels of 5-S-CD and 6H5M12C are less than 2.22 ng/ml and 1.04 ng/ml, respectively; b) that the group with the normal 6H5MI2C plasma level does not have any metastasis, whereas a normal 5-S-CD level is seen in both non-melanoma and melanoma patients with and without metastasis; c) that a high plasma 6H5MI2C level is seen in all melanoma patients with tumor thickness more than 3.0 mm regardless of the presence or absence of metastasis, whereas in thinner melanoma patients this is seen only in positive metastasis group; and d) that all melanoma patients with positive metastases showed a high plasma 6H5MI2C level (more than 1.75 ng/ml). We conclude that the measurement of plasma levels of melanin metabolites provides a method for detecting occult melanoma metastasis and estimating the prognosis of melanoma patients, plasma 6H5MI2C level being more sensitive and reliable than that of 5-S-CD, and its increased level being a high risk factor.