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Loss of E‐cadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance
Author(s) -
Chang Hsiao Wen,
Chow Vivian,
Lam King Yin,
Wei William Ignace,
Wing Yuen Anthony Po
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10211
Subject(s) - methylation , cancer research , dna methylation , downregulation and upregulation , cpg site , medicine , metastasis , pathology , immunohistochemistry , cadherin , primary tumor , tongue , carcinoma , cancer , biology , gene expression , cell , gene , biochemistry , genetics
BACKGROUND E‐cadherin is expressed on the surface of normal epithelial cells. Loss of E‐cadherin expression has been found in cancers and is postulated to facilitate tumor cell dissociation and metastasis. This study evaluated the role of promoter dense methylation in the downregulation of E‐cadherin expression in oral tongue carcinoma. METHODS E‐cadherin expression of 109 oral tongue carcinomas (93 primary tumors, 7 locally recurrent tumors, and 9 metastatic lymph nodes) was evaluated by immunohistochemical staining of tumor tissues. The methylation status of the CpG islands at the promoter region of E‐cadherin which flanked five HpaII (methylation sensitive restriction enzyme) digestion sites were evaluated by methylation sensitive polymerase chain reaction in 86 tumors (70 primary tumors, 7 locally recurrent tumors, and 9 metastatic lymph nodes). RESULTS Underexpression of E‐cadherin was found in 83% of primary tumors, 86% of recurrent tumors, and 89% of nodal metastases. Hypermethylated E‐cadherin promoter was found in 64% of primary tumors, 71% of recurrent tumors, and 67% of nodal metastases. Downregulation of E‐cadherin expression was found to be related to promoter hypermethylation. Consistently weak expression of E‐cadherin by promoter hypermethylation was observed in primary tumors, their corresponding metastatic lymph nodes, and recurrent tumors. Downregulation of E‐cadherin expression was a significant poor prognostic factor for survival. CONCLUSIONS Methylation of CpG sites at the promoter region played a key role in the inhibition of E‐cadherin expression in both primary oral tongue carcinomas and their corresponding recurrences and nodal metastases. The resulting downregulation of E‐cadherin expression had adverse effects on the prognosis of patients who were treated by primary surgery. Cancer 2002;94:386–92. © 2002 American Cancer Society.