Loss of E-cadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance

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 F-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 hypormethylation. 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. (C) 2002 American Cancer Society.