title: Metallothionein - overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients.
abstract: 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 chi2 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.
authors.affiliation: Clinical Department of Dermatology and Venerology, Innsbruck Medical University, Anichstrasse 35, Innsbruck A-6020, Austria. georg.weinlich@uibk.ac.at
authors.forename: G
authors.initials: G
authors.lastname: Weinlich
authors.forename: K
authors.initials: K
authors.lastname: Eisendle
authors.forename: E
authors.initials: E
authors.lastname: Hassler
authors.forename: M
authors.initials: M
authors.lastname: Baltaci
authors.forename: P O
authors.initials: PO
authors.lastname: Fritsch
authors.forename: B
authors.initials: B
authors.lastname: Zelger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D008668:Metallothionein / Q000096:biosynthesis*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D008668:Metallothionein