The prognostic significance of immunohistochemically detectable metallothionein in primary breast carcinomas.

Metallothionein (MT) is a low-molecular-weight protein with a high affinity for group II metal ions, especially zinc and copper. MT serves as an intracellular reservoir of these ions, but may also be involved in the detoxification of certain toxic metal ions such as cadmium. In addition, high MT contents might protect tumour cells from alkylating agents and irradiation. The aim of this study was to evaluate the prognostic significance of immunohistochemically detected MT overexpression in patients with primary breast carcinoma: 478 patients with primary breast carcinoma diagnosed during the period 1980-1985 were included. Formalin-fixed and paraffin-embedded tissue was used. Immunoreactivity for MT was found to be independent of the length of formalin fixation if the sections were microwave processed before incubation with the primary antibody. Patients were divided into two groups: those with MT overexpression (more than 10% positive tumour cells) and those with low expression (less than 10% positive tumour cells). MT overexpression was correlated with postmenopausal status, large tumour size, presence of lymph node metastases, high number of mitoses, severe nuclear pleomorphism, high histological grade (poor differentiation), and absence of PgR. In univariate analysis of survival data, MT overexpression was a predictor of poor overall survival in the entire group of patients. In multivariate analysis, MT overexpression failed to be of prognostic significance, whereas classical histopathological parameters such as tumour size, histological grade, and PgR were of independent prognostic significance.