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

Cancer. 2002 Jan 15;94(2):386-92. doi: 10.1002/cncr.10211.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics*
  • Cadherins / metabolism
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • CpG Islands
  • DNA Methylation*
  • DNA Primers
  • DNA, Neoplasm / chemistry
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics*
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology


  • Cadherins
  • DNA Primers
  • DNA, Neoplasm