Immunohistochemical localization of metallothionein in human breast cancerin comparison with cathepsin D, stromelysin-1, CD44, extracellular matrix components, p53, Rb, C-erbB-2, EGFR, steroid receptor content and proliferation

Metallothionein (MT) is a low molecular weight, cysteine-I-ich, zinc-bindin g protein that may have a function in cellular repair processes, growth and differentiation. Using a monoclonal antibody (E9) to metallothionein, we i nvestigated the immunohistochemical expression of MT in routinely fixed and paraffin-embedded tissue from 98 cases of female breast carcinomas. The MT expression was studied in comparison with the expression of the basement m embrane (BM) antigens (type IV collagen, laminin), fibronectin, cathepsin D , adhesion molecule CD44, p53 protein, the pRb, c-erbB-2 oncoprotein, EGFR, stromelysin-1, proliferation indices (Ki-67, PCNA), steroid receptor conte nt as well as with other conventional clinicopathological parameters of bre ast cancer. Strong MT expression was observed in the majority of tumour cel ls in 18.4 % of tumours focal MT positivity in 13.3 % and almost complete l ack of MT expression in 68.4% of cases (mean value 33.36 +/- 26.36). The MT expression in carcinoma cells was strongly associated with the DCIS compon ent of the tumour (p<0.0001). High values of MT were correlated with low st eroid receptor status (p=0.08 for ER receptor and p=0.019 for PgR receptor content). MT positive cases were correlated with stromelysin-1 Expression ( p=0.059) and cathepsin? D (p=0.058). These findings suggest that MT express ion is characteristic of the Early phase of breast carcinogenesis, possibly regulated by hormones, and could be a new potential prognostic marker in b reast cancer.