Metallothionein - overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

Metallothioneins ( MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Between 1993 and 2004, 3386 patients with primary cutaneous melanoma were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin- embedded tissues. In all, 1270 patients could be followed up for further statistical analysis ( Fisher's exact test, Mantel - Haenszel chi(2) test, Kaplan - Meier curves). The MT data of disease- free interval and overall survival were compared univariately and multivariately in Cox regression analysis. Immunohistochemical overexpression of MT in tumour cells of patients with primary melanoma ( 310 of 1270; 24.4%) was associated with a higher risk for progression ( 117 of 167; 70.1%) and reduced survival ( 80 of 110; 72.7%) of the disease ( P < 0.0001). Similarly, Kaplan - Meier curves gave highly significant disadvantages for the MT- positive group. Univariate analysis ( relative risk 7.4; 95% confidence interval ( CI) 5.2 - 10.2; P < 0.0001 for progression; relative risk 7.1; 95% CI 4.7 - 10.9; P < 0.0001 for survival), as well as multivariate analysis with other prognostic markers resulted in MT overexpression as a highly significant and independent factor for prognosis in primary melanoma.