title: Association between hypermethylated tumor and paired surgical margins in head and neck squamous cell carcinomas.
abstract: OBJECTIVE
  Surgical margin status is reported to be a relevant prognostic factor in head and neck squamous cell carcinoma (HNSCC), associated with a high risk of local recurrence. This study examines whether gene-promoter hypermethylation could be detected in HNSCC surgical margins with no histologic evidence of malignancy, and if so, whether it reflects epigenetic events of primary tumors.
  
  
  METHODS
  Promoter methylation status of MGMT, p16, and DAP-K genes was evaluated by methylation-specific PCR in 20 primary HNSCC tumors. Histopathologically negative surgical margins of hypermethylated tumors were collected, and their methylation status compared with the primary tumor status.
  
  
  RESULTS
  Promoter hypermethylation in at least one of the three tested genes was detected in 65% (13 of 20) of tumors. MGMT was hypermethylated in 50% (10 of 20), DAP-K in 45% (9 of 20), and p16 in 20% (4 of 20) of tumors. Methylation status was analyzed in 35 margins from 11 of 13 patients showing promoter hypermethylation in the tumor tissue. Identical methylation events were seen for at least one gene in primary tumor and surgical margins in 9 of 11 cases (82%). Association was found for gene-specific hypermethylation status in tumors and paired surgical margins, and gene-specific concordance was 63% for MGMT (kappa = 0.24), 90% for DAP-K (kappa = 0.74), and 90% for p16 (kappa = 0.79).
  
  
  CONCLUSIONS
  Our results support the hypothesis that detection of gene promoter hypermethylation in HNSCC tumor cells-free surgical margins may be a helpful biomarker to identify molecularly altered fields in areas adjacent to the tumor.
authors.affiliation: Division of Otorhinolaryngology, Department of Clinical Physiopathology, University of Turin, Italy. tiziana.martone@unito.it
authors.forename: Tiziana
authors.initials: T
authors.lastname: Martone
authors.forename: Anna
authors.initials: A
authors.lastname: Gillio-Tos
authors.forename: Laura
authors.initials: L
authors.lastname: De Marco
authors.forename: Valentina
authors.initials: V
authors.lastname: Fiano
authors.forename: Milena
authors.initials: M
authors.lastname: Maule
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalot
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Garzaro
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cortesina
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D019175:DNA Methylation; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic