 Methylation status of E-cadherin gene and its correlation to histological grade of malignancy in adenoid cystic carcinoma
S Maruya,MD,a H Kurotaki,MD,a H Shinkawa,MD,b S Yagihashi,MD,a
aDepartment of Pathology and bOtolaryngology,University of Hirosaki University
AIM: Adenoid cystic carcinoma (ACC) is a common malignant tumor in the salivary gland featured by indolent and prolonged clinical course with a high incidence of recurrence and metastasis. To explore the molecular mechanism for the invasive behavior of ACC, we investigated the E-cadherin expression and status of its gene in 26 cases of ACC and the effect of demethylating agent on ACC cell line in vitro. METHODS: E-cadherin expression was immunohistochemically examined on formalin-fixed paraffin sections. Cases were scored as negative, mixed or positive. DNAs extracted from the same tissues were used for methylation specific PCR. ACC3 cells cultured in the medium with or without 10mM 5-azacytidine were examined for the expression of mRNA and protein using RT-PCR, Western blot, and immunofluorescence. RESULTS: Methylation of CpG island of E-cadherin gene was detected in 16 of 23 primary ACC (70%) and 2 of 3 recurrence or metastasis (67%) that were associated with reduced expression of immunoreactive E-cadherin. Positive expressions of immunoreactive E-cadherin were depicted in 6 of 7 (86%) cases with low grade, 6 of 11 (55%) with intermediate, and 1 of 5 (20%) with high grade malignancy. ACC3 cells treated with 5-azacytidine showed increased expressions of mRNA and protein. CONCLUSIONS: E-cadherin gene is frequently methylated in ACC. Expression of E-cadherin is affected by gene hypermethylation in vitro. This epigenetic change of E-cadherin may be a major molecular mechanism for the invasive character of ACC.
KEY WORDS:
adenoid cystic carcinoma,
head and neck,
E-cadherin,
hypermethylation,
5-azacytidine.
For more information, contact maruya@cc.hirosaki-u.ac.jp
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Gene Expression, Part 1.
This presentation received an honorable mention in our poster contest and was recognized with the Symposium Presidents' Award for Scientific Excellence.
http://www.cancerprev.org/Journal/Issues/26/101/993/4235
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