Cysteine and indole derivatives as markers for malignant melanoma

Malignant melanoma is a skin tumour, which carries a very unfavourable prognosis. The early detection of a melanoma and even more its metastasis is of decisive importance for the survival prognosis of the patients. So there is always a desire for simple, economical and meaningful serological markers. From the cysteine- and indole-related derivatives, 5-S-cysteinyldopa (5-SCD) and 6-hydroxy-5-methoxy-indole-2-carboxylic acid (6H5MI2C) are the most important substances for this purpose. For 5-SCD, the sample pretreatment was carried out either by a manual extraction onto alumina, by an automated method onto boronic acid affinity gels or by an automated solid-phase extraction. For 6H5MI2C, liquid–liquid extractions or direct injection techniques were applied. The chromatographic analyses in the early years were mostly performed with GC–MS. Today HPLC is the nearly exclusively used separation technique. For HPLC, standard RP18 separating columns and usual compositions of eluents were applied. As detectors both the ECD and the FD showed a sufficient sensitivity and selectivity. 5-SCD and 6H5MI2C are very sensitive to light and oxidation. These properties must be taken into account in the complete analysis procedure, including the sample collection, otherwise false low values will result especially for plasma samples. For a critical discussion of the analytical methods and still more for the interpretation of the obtained results, the detailed analytical procedures must be considered. 5-SCD in plasma is one of the best markers of malignant melanoma. It shows an excellent specificity and also an adequate sensitivity in the metastatic melanoma stages. For the detection of primary melanomas and for urine instead of plasma samples, the sensitivity of 5-SCD is generally lower. Altogether, the sensitivity of this parameter is not yet sufficient. 6H5MI2C and other indole derivatives have been investigated far less than 5-SCD. 6H5MI2C correlates less clearly with the different stages of the melanoma and is therefore a less suitable marker. To improve the sensitivity of the findings, in future the investigations should be performed as multi-marker analysis with the simultaneous measurements of more than one marker substance in a given patient sample. Not only one measurement should be carried out per patient, it would be more meaningful to observe the patients with laboratory diagnostics in the follow-up.