title: Comparison of phaeomelanin and its precursor 5-S-cysteinyldopa in the serum of melanoma patients.
abstract: 5-S-Cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. Recently we have shown that the serum level of 5-S-CD is a sensitive and specific marker in predicting distant metastases. In melanocytes and melanoma cells, cysteinyldopa isomers are oxidized to phaeomelanin, the yellow to reddish melanin pigment. In this study we have developed a new method to measure levels of phaeomelanin in serum samples and have evaluated its clinical significance. The method is based on the production of 4-amino-3-hydroxyphenylalanine (4-AHP) and 3-amino-4-hydroxyphenylalanine (3-AHP) on reductive hydrolysis of phaeomelanin with hydriodic acid. 3-AHP is also derived from 3-nitrotyrosine-containing proteins. The isomeric 4-AHP and 3-AHP can be separated by high performance liquid chromatography. The mean +/- SD serum levels of 5-S-CD in control subjects (n = 36), in melanoma patients without recurrence (n = 92) and in melanoma patients with metastases (n = 24) were 2.7 +/- 1.2 nM (median 2.3 nM), 4.0 +/- 1.6 nM (median 3.8 nM) and 72 +/- 105 nM (median 35 nM), respectively. The serum levels of 4-AHP in these three groups were 45 +/- 21 nM (median 31 nM), 80 +/- 75 nM (median 53 nM) and 306 +/- 627 nM (median 133 nM), respectively. The serum levels of 4-AHP in patients with metastases (100 samples from 15 patients with progressive disease) correlated well (r = 0.887) with serum levels of 5-S-CD, while serum levels of 3-AHP did not (r = 0.240). The serum 5-S-CD and 4-AHP levels were serially analysed in the 15 patients with progressive disease. In two patients (13%), serum 4-AHP levels were elevated to abnormal levels before the serum 5-S-CD levels exceeded the cut-off value of 10 nM. In five patients (33%), the serum 4-AHP levels rose concurrently with the serum 5-S-CD levels. In the remaining eight patients (54%), serum 4-AHP levels were of less diagnostic value. Thus, the serum phaeomelanin level appears to be less sensitive than the serum 5-S-CD level in detecting distant metastases.
authors.affiliation: Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Mika
authors.initials: M
authors.lastname: Yokochi
authors.forename: Akiko
authors.initials: A
authors.lastname: Naito
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kageshita
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003548:Cysteinyldopa / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008543:Melanins / Q000097:blood*; D008545:Melanoma / Q000097:blood* / Q000556:secondary; D008875:Middle Aged; D044967:Serum / Q000737:chemistry; D012878:Skin Neoplasms / Q000097:blood*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D008543:Melanins; C016042:phaeomelanin; D003548:Cysteinyldopa; D014443:Tyrosine; C071227:4-amino-3-hydroxyphenylalanine