Evaluation of melanin-related metabolites as markers of melanoma progression.
BACKGROUND
Urinary excretion of 5-S-cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. Melanomas produce not only 5-S-CD but also 5,6-dihydroxyindole-2-carboxylic acid (5,6DHI2C) as major intermediates in melanin formation. 5,6DHI2C is then metabolized to the two O-methyl derivatives, 5H6MI2C and 6H5MI2C. The aim of this study was to determine which marker in serum and urine most sensitively reflected the progression of melanoma.


METHODS
Serum and 24-hour urine samples were collected and assayed serially by high-performance liquid chromatography every 1 to 4 months in 28 patients with primary or recurrent melanomas, for up to 48 months.


RESULTS
Serum concentration and urinary excretion of 5-S-CD and 6H5MI2C in patients with melanoma without metastases were close to those obtained from normal subjects. Metastases developed in 9 of the 28 patients. In seven of these nine patients, serum or urinary 5-S-CD values were elevated before or at the time of clinical detection of visceral metastases. However, serum 5-S-CD was elevated significantly earlier and reflected melanoma progression better than the physical examination and/or laboratory tests, such as scintigraphy and echography. Serum 6H5MI2C values exceeded the normal range shortly before death in three patients, and urinary 6H5MI2C did not increase at any stage in most patients, therefore these metabolites did not reflect progression of disease.


CONCLUSIONS
Among the four markers, serum 5-S-CD appears to be the best biochemical marker for the detection of progression of melanotic melanoma, a value of more than 10 nmol/l suggesting the presence of metastasis.
Horikoshi
T
T
Department of Dermatology, Sapporo Medical University, Japan.
Ito
S
S
Wakamatsu
K
K
Onodera
H
H
Eguchi
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D003548:Cysteinyldopa / Q000032:analysis* / Q000097:blood; D005260:Female; D006801:Humans; D007211:Indoles / Q000032:analysis*; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000175:diagnosis / Q000473:pathology*
D014408:Biomarkers, Tumor; D007211:Indoles; D003548:Cysteinyldopa; C017407:5-hydroxy-6-methoxy-2-indolylcarboxylic acid; C030692:5,6-dihydroxy-2-indolylcarboxylic acid