Metallothionein and apoptosis in primary human hepatocellular carcinoma (HCC) from northern China

Abstract

Background: Metallothionein (MT), acting as an antioxidant and zinc binding protein, may play an important role in regulation of apoptosis. Its differential expression has been documented in various human tumours.

Materials and methods: MT expression by immunohistochemical staining with a polyclonal antibody and apoptotic cells (APC) by TUNEL technique were investigated in 20 cases of hepatocellular carcinoma (HCC) and 2 normal livers from Northern China. Adjacent normal liver was available from 9 of these cases and 6 had adjacent cirrhotic tissue. There was no difference for MT staining and incidence of APC between normal liver and adjacent normal liver, and thus both were used as control liver.

Results: Control liver had consistent MT staining with very low incidence of APC. Adjacent cirrhotic liver showed the same intensity of MT staining, with a similar incidence of APC to control liver. Twelve of 20 HCC cases (60%) showed no MT staining, and the rest also showed a low grade of MT staining as compared with control or adjacent cirrhotic livers. The incidence of APC in HCC was markedly higher than that in control liver or adjacent cirrhotic liver. The negative correlation of numbers of APC with MT expression was statistically significant (p < 0.005). The high incidence of APC in liver with a low MT expression was confirmed in double staining for MT and APC.

Conclusions: The present investigation from Northern Chinese samples has shown that MT expression in HCC was different from that in other human tumours, such as breast carcinoma. This suggests a different pattern of expression of MT protein in these two kinds of cancer. This investigation is important in understanding the mechanisms of the drug resistance of tumour cells, and may help to design better treatment strategies.