EVALUATION OF MELANIN-RELATED METABOLITES AS MARKERS OF MELANOMA PROGRESSION

Background. Urinary excretion of 5-S-cysteinyldopa (5-S-CD) has been u sed as a biochemical marker of melanoma progression. Melanomas produce not only 5-S-CD but also 5,6-dihydroxyindole-2-carboxylic acid (5,6DH I2C) as major intermediates in melanin formation. 5,6DHI2C is then met abolized to the two O-methyl derivatives, 5H6MI2C and 6H5MI2C. The aim of this study was to determine which marker in serum and urine most s ensitively reflected the progression of melanoma. Methods. Serum and 2 4-hour urine samples were collected and assayed serially by high-perfo rmance liquid chromatography every 1 to 4 months in 28 patients with p rimary or recurrent melanomas, for up to 48 months. Results. Serum con centration and urinary excretion of 5-S-CD and 6H5MI2C in patients wit h melanoma without metastases were close to those obtained from normal subjects. Metastases developed in 9 of the 28 patients. In seven of t hese nine patients, serum or urinary 5-S-CD values were elevated befor e or at the time of clinical detection of visceral metastases. However , serum 5-S-CD was elevated significantly earlier and reflected melano ma progression better than the physical examination and/or laboratory tests, such as scintigraphy and echography. Serum 6H5MI2C values excee ded the normal range shortly before death in three patients, and urina ry 6H5MI2C did not increase at any stage in most patients, therefore t hese metabolites did not reflect progression of disease. Conclusions. Among the four markers, serum 5-S-CD appears to be the best biochemica l marker for the detection of progression of melanotic melanoma, a val ue of more than 10 nmol/l suggesting the presence of metastasis.