IMMUNOHISTOCHEMICALLY DEMONSTRATED METALLOTHIONEIN EXPRESSION IN MALIGNANT-MELANOMA

Metallothioneins are ubiquitous proteins with a high affinity for heav y metal ions, e.g. zinc, copper and cadmium. Experimentally, metalloth ionein over-expression in cell lines derived from a variety of cancers has been associated with resistance to anticancer drugs and irradiati on therapy. Using a monoclonal antibody (E9) to metallothionein we inv estigated immunoreactive expression in routinely fixed and paraffin-em bedded tissue from 63 cases of malignant melanoma and 13 secondary dep osits. Whereas a variety of cells in normal skin showed metallothionei n expression, all forms of benign naevi studied were uniformly negativ e. In contrast 13/30 'thin' (less-than-or-equal-to 1.5 mm; 0.7 +/- 0.4 ), 25/29 'thick' malignant melanoma (> 1.5 mm; 5.5 +/- 3.9) and 12/13 metastases were positive. Six patients with thin and 19 with thick mel anoma with metallothionein expression died during a mean observation p eriod of 6.4 +/- 1.8 and 3.6 +/- 2.5 years, respectively, their surviv al distribution function analyses giving statistically significant res ults for both the vertical tumour thickness (P<0.0001) and metallothio nein expression (P< 0.0001). These immunohistochemical results, based on routinely processed paraffin-embedded tissue, suggest that metallot hionein expression in malignant melanoma is significantly associated w ith progressive disease and might therefore be a useful prognostic ind icator.