Age‐related changes in metallothionein, copper, copper‐associated protein, and lipofuscin in human liver: A histochemical and immunohistochemical study

The relationship between immunohistochemically demonstrable hepatic metallothionein (MT) and age was studied in histologically normal livers from 12 fetuses (13–28 weeks' gestation) and 19 children (birth‐4 years). In addition, the relationships between copper (rubeanic acid‐positive), copper‐associated protein (orcein‐positive), lipofuscin (periodic acid Schiff after diastase digestion and Schmorls‐positive), and MT (immunostaining) were studied. The fetal livers showed periportal and patchy mid‐zone copper‐associated protein and lipofuscin granules, together with strong diffuse cytoplasmic and nuclear MT immunostaining. On the other hand, the livers of the children over 6 months of age showed no copper‐associated protein or lipofuscin granules, and minimal or no cytoplasmic MT immunostaining (one case showed nuclear MT immunostaining). The DPAS and Schmorls‐positive lipofuscin granules appeared to be identical to the orcein‐positive copper‐associated protein granules which were consistently negative on MT immunostaining. The demonstration of cytoplasmic granular orcein positivity or diffuse non‐granular MT immunostaining in liver above the age of 6 months would appear to be of pathological significance.