Promoter methylation as a common mechanism for inactivating E-cadherin in human salivary gland adenoid cystic carcinoma
✍ Scribed by Chun-Ye Zhang; Li Mao; Lei Li; Zhen Tian; Xiao-Jian Zhou; Zhi-Yuan Zhang; Jiang Li
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 556 KB
- Volume
- 110
- Category
- Article
- ISSN
- 0008-543X
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
BACKGROUND.
The role of promoter methylation in the inactivation of E‐cadherin (E‐cad) in salivary gland adenoid cystic carcinoma (ACC) is unknown. The objective of this study was to determine the role and potential clinical implications of promoter methylation of E‐cad in salivary gland ACC.
METHODS.
The promoter methylation status of E‐cad was determined by using methylation‐specific polymerase chain reaction (PCR) analysis in 60 primary salivary gland ACC tissues and 3 ACC cell lines. The level of E‐cad protein expression was determined by immunohistochemical analysis of each tumor. E‐cad protein and messenger RNA (mRNA) expression levels were examined by immunohistochemical analysis and reverse transcriptase‐PCR in 3 ACC cell lines. Associations between molecular alterations and patients' clinicopathologic characteristics were analyzed statistically. E‐cad mRNA expression was examined in a 5‐azacytidine‐treated ACC‐2 cell line.
RESULTS.
Promoter methylation of E‐cad was detected in 34 of 60 tumors (57%). Of those 34 tumors, 18 tumors (53%) showed no E‐cad protein expression, whereas only 5 of the remaining 26 tumors (19%) without E‐cad promoter methylation showed no E‐cad protein expression (P = .01). Tumors that had E‐cad promoter methylation had a significantly higher histologic grade (P = .01) and more perineural invasion (P = .02) compared with tumors that did not have methylation. All 3 ACC cell lines exhibited E‐cad promoter methylation and a lack of E‐cad mRNA and protein expression, whereas 5‐azacytidine restoredE‐cad mRNA expression in the ACC‐2 cell line.
CONCLUSIONS.
E‐cad frequently is inactivated in salivary gland ACC through promoter methylation, and E‐cad promoter methylation may play a role in tumor cell differentiation and perineural invasion. Cancer 2007. © 2007 American Cancer Society.