title: Loss of E-cadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance.
abstract: 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.
authors.affiliation: Department of Surgery, The University of Hong Kong, Queen Mary Hospital, SAR China.
authors.forename: Hsiao Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Vivian
authors.initials: V
authors.lastname: Chow
authors.forename: King Yin
authors.initials: KY
authors.lastname: Lam
authors.forename: William Ignace
authors.initials: WI
authors.lastname: Wei
authors.forename: AnthonyPoWing
authors.initials: A
authors.lastname: Yuen
mesh_terms: D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000737:chemistry; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D015820:Cadherins; D017931:DNA Primers; D004273:DNA, Neoplasm