1. ¹Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan
2. ²Department of Otorhinolaryngology, Hirosaki University School of Medicine, Hirosaki, Japan
3. ³Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Correspondence: Dr S Yagihashi, Department of Pathology, Hirosaki University, 5 Zaifucho, Hirosaki 036-8562, Japan. E-mail: yagihasi@cc.hirosaki-u.ac.jp

Received 8 November 2003; Revised 5 January 2004; Accepted 18 January 2004; Published online 26 March 2004.

Abstract

Adenoid cystic carcinoma, a relatively uncommon tumor of salivary glands, is characterized by a prolonged clinical course and a fatal outcome. The molecular events underlying their progression are unknown. In this study, we examined the methylation status of E-cadherin gene and its protein expression in 23 cases of adenoid cystic carcinoma and correlated the results with the clinicopathologic factors to determine its role in these tumors. We also analyzed the effect of 5-azacytidine on the re-expression in a methylated cell line of adenoid cystic carcinoma for this gene. In our study, E-cadherin immunoreactivity, although heterogeneous, showed a progressive reduction with high histological grade and in metastatic and recurrent lesions. Promoter methylation was detected in 16 of 23 cases (70%), but there was no correlation with the histological grade or patient prognosis. Microdissection of immuno-negative cells in heterogeneous tumors showed positive methlyation. In the cell line from salivary adenoid cystic carcinoma with methylated E-cadherin, 5-azacytidine restored the E-cadherin expression. Our results indicate that: (1) E-cadherin gene promoter is frequently methylated in adenoid cystic carcinoma, leading to reduced E-cadherin expression, (2) variable E-cadherin expression might result from the intratumoral heterogeneity, and (3) increased extent of methylated areas may be associated with progression and advancement of the disease.