title: Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance.
abstract: OBJECTIVE
  Hypermethylation of tumor suppressor gene promoters has been found in head and neck squamous carcinoma (HNSCC) and other solid tumors. We evaluated these alterations in pretreatment salivary rinses from HNSCC patients by using real-time quantitative methylation-specific PCR (Q-MSP).
  
  
  METHODS
  Pretreatment saliva DNA samples from HNSCC patients were evaluated for patterns of hypermethylation by using Q-MSP. Target tumor suppressor gene promoter regions were selected based on a previous study describing a screening panel for HNSCC in a high-risk population subjects. The selected genes were: DAPK, DCC, MINT-31, TIMP-3, p16, MGMT, CCNA1.
  
  
  RESULTS
  We analyzed the panel in a cohort of 61 HNSCC patients. Thirty-three of the analyzed patients (54.1%) showed methylation of at least one of the selected genes in the saliva DNA. Pretreatment methylated saliva DNA was not significantly associated with tumor site (P = 0.209) nor clinical stage (P = 0.299). However, local disease control and overall survival were significantly lower in patients presenting hypermethylation in saliva rinses (P = 0.010 and P = 0.015, respectively). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (HR = 12.2; 95% CI = 1.8-80.6; P = 0.010) and overall survival (HR = 2.8; 95% CI = 1.2-6.5; P = 0.016).
  
  
  CONCLUSIONS
  We were able to confirm an elevated rate of promoter hypermethylation in HNSCC saliva of patients by using a panel of gene promoters previously described as methylated specifically in HNSCC. Detection of hypermethylation in pretreatment saliva DNA seems to be predictive of local recurrence and overall survival. This finding has potential to influence treatment and surveillance of HNSCC patients.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
authors.forename: André Lopes
authors.initials: AL
authors.lastname: Carvalho
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.forename: Carmen
authors.initials: C
authors.lastname: Jeronimo
authors.forename: Chetan S
authors.initials: CS
authors.lastname: Nayak
authors.forename: Ashok N
authors.initials: AN
authors.lastname: Reddy
authors.forename: Mohammad O
authors.initials: MO
authors.lastname: Hoque
authors.forename: Steven
authors.initials: S
authors.lastname: Chang
authors.forename: Mariana
authors.initials: M
authors.lastname: Brait
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Jiang
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kim
authors.forename: Quia
authors.initials: Q
authors.lastname: Claybourne
authors.forename: David
authors.initials: D
authors.lastname: Goldenberg
authors.forename: Zubair
authors.initials: Z
authors.lastname: Khan
authors.forename: Tanbir
authors.initials: T
authors.lastname: Khan
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Wayne
authors.initials: W
authors.lastname: Koch
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012463:Saliva / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor