M. Fresno et al., LOCALIZATION OF METALLOTHIONEIN IN BREAST CARCINOMAS - AN IMMUNOHISTOCHEMICAL STUDY, Virchows Archiv. A. Pathological anatomy and histology, 423(3), 1993, pp. 215-219
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.