Evaluation of 5-S-cysteinyldopa as a marker of melanoma progression: 10 years’ experience

Abstract

5-S-Cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. In this study, we measured serum levels of 5-S-CD in 2648 samples taken from 218 patients in order to evaluate the usefulness of this parameter in following melanoma progression and prognosis. 5-S-CD levels were significantly elevated above the upper limit of the normal range (10 nmol/l) in stage IV melanoma patients. The sensitivity of elevated serum 5-S-CD levels in detecting distant metastasis was 73%, while the specificity was 98% and the positive predictive value 94%. The sensitivity was improved to 77% when cases of amelanotic melanoma were excluded. Patients without metastases had elevated 5-S-CD values in 5% of the 1480 serum samples. Changes in serum 5-S-CD levels were followed during disease progression until the end stage in 49 patients. In 33% of the patients, elevation of serum 5-S-CD levels preceded clinical detection of visceral metastases, and in 37% elevation of 5-S-CD levels occurred at the same time as visceral metastasis. Patients with elevated 5-S-CD levels before or after surgical treatment had significantly shorter survival times than those with normal levels. These results show that the level of 5-S-CD in the serum is a sensitive and specific marker in predicting distant metastases. Elevated serum levels of 5-S-CD, before or after surgical treatment, is associated with a poor prognosis.

Highly Sensitive Detection of Melanoma at an Early Stage Based on the Increased Serum Secreted Protein Acidic and Rich in Cysteine and Glypican-3 Levels

“…We next compared the serum concentrations of SPARC, GPC3, and 5-S-cysteinyldopa in patients with melanoma classified by clinical stage (Tables 1 and 2). We fixed the cutoff level at 1 unit/mL in GPC3 and at 10 nmol/L in 5-S-cysteinyldopa as reported (6,10). Figure 2E shows the serum concentrations of SPARC quantified by ELISA in 109 melanoma patients classified by stage.…”

Neuroendocrine Functions of Melanocytes: Beyond the Skin-Deep Melanin Maker

“…Melanocytes and melanoma cells actively secrete DOPA and various melanin-related metabolites, such as 5-S-cysteinyldopa, into the blood, some of which are eventually excreted into urine (Agrup et al 1979;Wakamatsu and Ito 1995;Wakamatsu et al 2002. Moreover, the urinary levels of eumelanin metabolites vary in humans depending on seasons, with the highest level in July and the lowest level in December .…”

Biomarkers for Melanoma Diagnosis and the Technologies Used to Identify Them

“…Of the urinary biomarkers of melanoma already identified (Table 3), 5SCD and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C), are intermediate metabolites in melanin pigment formation, and have been the most extensively studied. An increase in urine levels of these markers has been associated with tumor progression and low survival rates (Kärnell et al, 1997;Bánfalvi et al, 2000;Wakamatsu et al, 2002). In healthy patients, the urinary levels of these markers are influenced by age (Meyerhöffer et al, 1998), sex (Morishima and Hanawa, 1981;Kågedal et al, 1992), skin color and season (Ito et al, 1987), but not by pregnancy (Carstam et al, 1985).…”

“…Moreover, the 90-kDa glycoprotein (TA-90) (Rote et al, 1980;Euhus et al, 1989), S100A7 (Brouard et al, 2002) and β-human chorionic gonadotropin (Carter et al, 1995) have also been identified in the urine of patients with melanoma (Table 3). Of these urinary biomarkers, 5SCD, 6H5MI2C, and S100A7 can be considered the most melanoma-specific of the urinary biomarkers (Kärnell et al, 1997;Bánfalvi et al, 2000;Brouard et al, 2002;Wakamatsu et al, 2002 An indicator for liver metastasis; a prognostic indicator in metastatic melanoma Deichmann et al, 2000;Findeisen et al, 2009;Zhuang et al, 2010 Glypican-3 (GPC3) Unknown exactly, but may function as a survival or proliferation-associated factor Nakatsura et al, 2004;Ikuta et al, 2005 PKCα A survival or proliferation-associated protein Kang et al, 2009 5SCD A precursor of melanin; Increased in metastatic prognosis Kärnell et al, 1997Kärnell et al, , 2000Bánfalvi et al, 2000;Wakamatsu et al, 2002 6H5MI2C A precursor of melanin; Increased in metastatic prognosis Hara et al, 1994;Kärnell et al, 1997 A superfamily of acute-phase proteins and proinflammatory adipokine Findeisen et al, 2009 Cystatin C A potent inhibitor of cysteine proteases; Increased primary and metastatic melanoma Kos et al, 1997;Ervin and Cox, 2005 Biomarkers References 5SCD Yamada et al, 1992;Kärnell et al, 1997;Bánfalvi et al, 2000;Wakamatsu et al, 20026H5MI2C Yamada et al, 1992Kärnell et al, 1997TA-90 Rote et al, 1980Euhus et al, 1989…”