Expression of metallothionein‐1 and metallothionein‐2 as a prognostic marker in hepatocellular carcinoma

BACKGROUND AND AIMS: Metallothionein (MT)-1 and -2 are low-molecular weight, cysteine-rich, intracellular metal-binding proteins involved in diverse functions, such as metal homeostasis, cell cycle progression, cell differentiation, and carcinogenesis. This study investigated the expression of MT-1 and MT-2 as a prognostic marker in hepatocellular carcinoma (HCC). METHODS: Expression of MT-1 and MT-2 were evaluated immunohistochemically in tissue microarrays containing samples from 370 HCCs, 336 adjacent noncancerous livers, and 12 normal livers. The relationships between MT-1 and MT-2 expression and the clinicopathological parameters of HCC were assessed. RESULTS: The expression of MT-1 and MT-2 was uniformly strong in the nucleus and cytoplasm of normal liver, but varied in noncancerous livers and HCCs. Loss of nuclear and cytoplasmic expression was significantly more in HCCs than in adjacent noncancerous livers (P < 0.001). The loss of nuclear expression of MT-1 and MT-2 was significantly correlated with high Edmondson-Steiner grade and the presence of microvascular invasion (P < 0.05 each). Multivariate analysis showed that the loss of nuclear expression of MT-1 and MT-2 was an independent poor prognostic factor for both recurrence-free survival and overall survival. CONCLUSIONS: The expression of MT-1 and MT-2 may play a role in HCC differentiation and carcinogenesis, and may predict prognosis in patients with HCC.