Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance

André Lopes Carvalho, Rui Henrique, Carmen Jeronimo, Chetan S. Nayak, Ashok N. Reddy, Mohammad O. Hoque, Steven Chang, Mariana Brait, Wei Wen Jiang, Michael M. Kim, Quia Claybourne, David Goldenberg, Zubair Khan, Tanbir Khan, William H. Westra, David Sidransky, Wayne Koch, Joseph A. Califano

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Purpose: 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). Experimental Design: 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.

Original languageEnglish (US)
Pages (from-to)4782-4789
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number14
DOIs
StatePublished - Jul 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Carvalho, A. L., Henrique, R., Jeronimo, C., Nayak, C. S., Reddy, A. N., Hoque, M. O., Chang, S., Brait, M., Jiang, W. W., Kim, M. M., Claybourne, Q., Goldenberg, D., Khan, Z., Khan, T., Westra, W. H., Sidransky, D., Koch, W., & Califano, J. A. (2011). Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance. Clinical Cancer Research, 17(14), 4782-4789. https://doi.org/10.1158/1078-0432.CCR-11-0324