title: Molecular staging of surgical margins in oral squamous cell carcinoma using promoter methylation of p16(INK4A), cytoglobin, E-cadherin, and TMEFF2.
abstract: BACKGROUND
  Local recurrence in oral squamous cell carcinoma (OSCC) despite clear surgical margins may indicate the presence of residual, sub-microscopic disease. Molecular assessment of surgical margins may provide a greater prognostic sensitivity compared to histopathology. We aimed to determine whether promoter methylation in deep and mucosal resection margins can predict recurrence in OSCC.
  
  
  METHODS
  Forty-eight consecutive OSCC cases were recruited and a 5 mm(3) tumor sample plus 5 deep and 5 mucosal margin samples were snap frozen. Clinical, pathological, adjuvant therapy, and outcome data were recorded. Tumors were informative if >5 % promoter methylation was found for ≥1 of 4 genes using qMSP. Margins were declared molecularly positive if >1 % promoter methylation was found in any margin.
  
  
  RESULTS
  Thirty (63 %) of 48 cases were methylation informative. Mucosal margin samples were largely positive for methylation (26 of 30, 87 %), indicating the presence of field cancerization. Methylation at ≥1 gene promoters in ≥1 deep margin correlated with the presence of close/involved mucosal margins (P = 0.027) and increased pT status (P = 0.027) but not the status of deep margins, recurrence, or survival.
  
  
  CONCLUSIONS
  The current gene panel did not add prognostic information to histopathological reporting of resection margins. Future efforts should concentrate on improving gene selection, informativity, and assay performance in the patient group with intermediate indications for adjuvant therapy.
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Shaw
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hobkirk
authors.forename: George
authors.initials: G
authors.lastname: Nikolaidis
authors.forename: Julia A
authors.initials: JA
authors.lastname: Woolgar
authors.forename: Asterios
authors.initials: A
authors.lastname: Triantafyllou
authors.forename: James S
authors.initials: JS
authors.lastname: Brown
authors.forename: Triantafillos
authors.initials: T
authors.lastname: Liloglou
authors.forename: Janet M
authors.initials: JM
authors.lastname: Risk
mesh_terms: D000368:Aged; D015820:Cadherins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000078842:Cytoglobin; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D005914:Globins / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009363:Neoplasm Proteins / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D018365:Neoplasm, Residual; D011401:Promoter Regions, Genetic
chemical_list: C000627265:CYGB protein, human; D015820:Cadherins; D000078842:Cytoglobin; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C423567:TMEFF2 protein, human; D005914:Globins