title: Cohypermethylation of p14 in combination with CADM1 or DCC as a recurrence-related prognostic indicator in stage I esophageal squamous cell carcinoma.
abstract: BACKGROUND
  The objective of this study was to discover molecular biomarkers associated with the recurrence of esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  The authors retrospectively analyzed the hypermethylation status of 11 genes using methylation-specific polymerase chain reaction (PCR) and the expression of epidermal growth factor receptor (EGFR), O-6 methylguanine-DNA methyltransferase (MGMT), tumor protein 53 (p53), and transforming growth factor β (TGFβ) using immunohistochemistry in 329 formalin-fixed, paraffin-embedded ESCCs.
  
  
  RESULTS
  Recurrence was identified in 151 of 329 ESCCs (46%) at a median follow-up of 4.5 years. The recurrence was associated with hypermethylation of the genes cell adhesion molecule 1 (CADM1) (P = .003), deleted in colon carcinoma (DCC) (P = .04), or cyclin-dependent kinase inhibitor 2A (p14) (P = .02) in patients with stage I ESCC. Thirty-six of 37 Stage I ESCCs (97%) that had cohypermethylation of at least 2 of the 3 genes had hypermethylation of p14 plus either CADM1 or DCC or both CADM1 and DCC. The 5-year recurrence-free survival (RFS) rates were 93% in patients who had stage I disease without hypermethylation of the 3 genes and 56% in those who had cohypermethylation of p14 in combination with CADM1 and/or DCC. Patients who had stage I ESCC with cohypermethylation of p14 in combination with DCC and/or CADM1 had 7.13 times (95% confidence interval, 1.61-31.64 times; P = .009) poorer RFS compared with those who had no hypermethylation of the 3 genes after adjusting confounding factors. Hypermethylation of the other 8 genes and altered expression of 4 proteins were not associated with recurrence across pathologic stages.
  
  
  CONCLUSIONS
  The current results suggested that cohypermethylation of p14 in combination with DCC and/or CADM1 may be an independent prognostic factor for recurrence in patients with stage I ESCC.
authors: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea.
authors: Eunju
authors: E
authors: Lee
authors: Bo Bin
authors: BB
authors: Lee
authors: Eunkyung
authors: E
authors: Ko
authors: Yujin
authors: Y
authors: Kim
authors: Jungho
authors: J
authors: Han
authors: Young Mog
authors: YM
authors: Shim
authors: Joobae
authors: J
authors: Park
authors: Duk-Hwan
authors: DH
authors: Kim
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics*; D000075389:DCC Receptor; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics*; D012189:Retrospective Studies; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D007136:Immunoglobulins; D011956:Receptors, Cell Surface; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins