Metallothionein-overexpression as a prognostic marker in melanoma

Malignant melanoma is one of the most aggressive human neoplasms and its incidence is still increasing. Prognoses for melanoma patients are currently based on statistical parameters. For estimating the risk for a possible progression and for overall survival, Breslow tumour thickness and the invasion level (Clark level) are the most established markers for melanomas at the time of the primary diagnosis. In thicker melanomas (>1 mm) the additional information about the status of the sentinel lymph-node (SLN) might be helpful. Nevertheless new prognostic parameters are needed, that will allow us to formulate more precise prognoses for the individual cases. The metallo-thionein family is a class of intracellular low-molecular-weight, cysteine-rich proteins with a high affinity for heavy-metal ions. They are involved in many (patho-) physiological processes and presumably play an important role in the carcinogenesis. In the last decades overexpression of immunohistochemically labelled metallothioneins (MTs) on paraffin-embedded tissues turned out as a highly significant prognostic marker in different tumours. This review summarizes the results of those studies, in which MT-overexpression was able to show a very high significance for progression and survival in melanoma patients. In contrast to most other progression markers, MT-overexpression is independent from tumour-thickness, and is highly specific even in thin (low risk) melanoma patients. Nowadays, in high risk melanoma patients sentinel lymph-node (SLN-) biopsy is performed, a surgical technique with predictive value for progression, the benefit of this procedure for the individual overall survival still remains unclear. In a study comparing SLN and MT-overexpression the results corroborate the validity of MT-overexpression in primary melanoma as a useful additional prognostic marker, accuracy is comparable although to some degree supplementary to the results of SLN biopsy.