1. ¹Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan
2. ²Department of Surgery I, Iwate Medical University School of Medicine, Morioka, Japan
3. ³Department of Internal Medicine I, Iwate Medical University School of Medicine, Morioka, Japan
4. ⁴Department of Dermatology, Iwate Medical University School of Medicine, Morioka, Japan

Correspondence: Dr C Maesawa, MD, Department of Pathology, Iwate Medical University School of Medicine, 020-8505 Morioka, Japan. E-mail: chihaya@iwate-med.ac.jp

Received 22 July 2004; Revised 7 October 2004; Accepted 11 October 2004; Published online 20 December 2004.

Abstract

We examined expression of maspin and the epigenetic status of its gene in 40 primary hepato-biliary tract carcinomas and 11 cell lines originating from hepato-pancreatico-biliary tract carcinomas. Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (22/25, 88%) but not in hepatocellular carcinomas (HCCs) (0/15, 0%). Aberrant maspin expression by five pancreatico-biliary tract carcinoma cell lines was closely associated with demethylation at the maspin promoter. Five of six HCC cell lines were maspin-negative and exhibited extensive hypomethylation and hypoacetylation at the maspin promoter. Treatment with 5-aza-2'-deoxycytidine did not activate maspin expression in these five maspin-negative HCC cell lines, whereas treatment with Trichostatin A (TSA) activated maspin expression in two of them. Treatment with TSA increased histone acetylation in some HCC cell lines. These results suggest that aberrant maspin expression in biliary tract carcinomas is closely associated with demethylation at the promoter region, but that some HCC cell lines additionally require histone acetylation. In addition, the fact that maspin-negative HCC cell lines remain after treatment with TSA suggests the existence of other repressive factors controlling maspin expression.