1. ¹Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
2. ²Pathology and tumour biology, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
3. ³Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

Correspondence: Professor Dr GA Meijer, Department of Pathology, VU University Medical Center, PO Box 7057, Amsterdam 1007 MB, The Netherlands. E-mail: ga.meijer@vumc.nl

⁴These authors have contributed equally to this work.

Received 3 September 2008; Revised 10 October 2008; Accepted 20 October 2008; Published online 11 November 2008.

Abstract

T-lymphocyte maturation associated protein, MAL, has been described as a tumour-suppressor gene with diagnostic value in colorectal and oesophageal cancers, and can be inactivated by promoter hypermethylation. The aim of this study was to analyse the prevalence of MAL promoter hypermethylation and the association with mRNA expression in gastric cancers and to correlate methylation status to clinicopathological data. Bisulphite-treated DNA isolated from formalin-fixed and paraffin-embedded samples of 202 gastric adenocarcinomas and 22 normal gastric mucosae was subjected to real-time methylation-specific PCR (Q-MSP). Two regions within the MAL promoter (M1 and M2) were analysed. In addition, 17 frozen gastric carcinomas and two gastric cancer cell lines were analysed both by Q-MSP and real-time RT–PCR. Methylation of M1 and M2 occurred in 71 and 80% of the gastric cancers, respectively, but not in normal gastric mucosa tissue. Hypermethylation of M2, but not M1, correlated with significantly better disease-free survival in a univariate (P=0.03) and multivariate analysis (P=0.03) and with downregulation of expression (P=0.01). These results indicate that MAL has a putative tumour-suppressor gene function in gastric cancer, and detection of promoter hypermethylation may be useful as a prognostic marker.