Downregulated expression of metallothionein and its clinicopathological significance in hepatocellular carcinoma

Abstract

Metallothionein (MT) protein is related to different stages of development and progression of various tumors in humans. The aim of the present study was to investigate expression and localization of MT and their association with clinicopathological characteristics in hepatocellular carcinoma (HCC). Histological specimens of 400 HCC with corresponding non-cancerous liver tissues were stained for MT (E9), P53 and Ki-67 by immunohistochemical staining using tissue microarrays. RNA expression of MT-1X and MT-2A isoforms was determined by real-time reverse transcription-polymerase chain reaction in a set of independent samples of 161 HCC. Downregulated expression of MT at both mRNA and protein levels was detected in HCC, compared with non-cancerous liver tissues. The frequencies of MT positivity were significantly lower in cases with positive hepatitis B surface antigen than in those with negative hepatitis B surfaceantigen (P = 0.042). The positive rate of MT expression was more frequent in tumors </=2 cm than in tumors >2 cm in diameter (P = 0.007). There was a tendency for MT expression to decrease with the progression of histological grade. Mainly nuclear expression of MT correlated with poorly differentiated HCC. No statistical correlation was found between P53, Ki-67 and MT expression. Downregulated expression of MT in HCC may play a role in hepatocarcinogenesis and be a marker of hepatocellular differentiation. Hepatitis B virus infection may be correlated to downregulated expression of MT. The mainly nuclear MT immunostaining may reflect an aggressive behavior in poorly differentiated HCC.