LOCALIZATION OF METALLOTHIONEIN IN BREAST CARCINOMAS - AN IMMUNOHISTOCHEMICAL STUDY

Metallothionein (MT) is a cysteine-rich, low molecular weight protein that binds zinc, copper, and cadmium. It is present in a number of nor mal cells including hepatocytes particularly during fetal and early po stnatal life. It has been suggested that developmental profile of MT i s similar to other oncofetal gene products and hence, it could be used as a marker for aggressive tumour behaviour. In order to test that hy pothesis, we used a monoclonal antibody to MT and immunohistochemicall y evaluated formalin-fixed, paraffin-embedded tissues from 79 breast c arcinomas. In nonneoplastic breast tissue, a strong nuclear and cytopl asmic staining was observed in myoepithelial cells. Positive staining for MT was present in 35 (44%) of breast carcinomas. In most positive cases, nuclear, or both nuclear and cytoplasmic staining was seen. All positive tumours were invasive ductal carcinomas, including a medulla ry and a metaplastic carcinoma. None of the mucinous, lobular, or intr aductal papillary carcinomas reacted for MT. A statistically significa nt association was found between MT immunostaining and histological gr ade (P<0.01) as well as with nuclear grade (P<0.01). We also observed an inverse relationship between MT staining and oestrogen receptor con tent of tumours (P<0.01). Similarly, a statistically significant assoc iation was found between moderate and strong MT immunostainig and decr eased overall survival and shorter disease-free survival (P<0.01). MT immunostaining was also predective of a worse prognosis in the subgrou p of lymph node negative (P<0.001) and oestrogen receptor negative pat ients (P<0.01). No statistically significant association was found bet ween MT staining and size of tumour or the presence of lymph node meta stasis. We conclude that MT staining may be a useful marker of less di fferentiated and more aggressive carcinomas of the breast.