DCC promoter hypermethylation in HNSCC and correlation with clinical parameters

Abstract

Problem: Hypermethylation of tumor suppressor gene promoters has been found in head and neck squamous cell carcinoma (HNSCC) and other solid tumors. We evaluated DCC promoter hypermethylation in HNSCC in a quantitative fashion using real-time quantitative MSP (Q-MSP) and evaluated its correlation with DCC expression and clinical parameters. Methods: Tumor DNA samples from 47 primary HNSCC as well as DNA from the saliva of 50 and sera of 20 control subjects were evaluated for patterns of DCC promoter hypermethylation using Q-MSP. Q-MSP for HNSC and controls was normalized using a âactin control and analyzed using appropriate statistical methods. Medical records of the patients were reviewed for collection of the clinical information. Results: DCC promoter hypermethylation was detected in 32 HNSCC (68.1%), but not in the saliva or serum DNA from the control subjects ( P < 0.001). DCC promoter hypermethylation was significantly associated with the consumption of alcohol ( P = 0.038). No association was observed regarding age ( P = 0.723), race ( P = 0.107), gender ( P = 0.057), consumption of tobacco ( P = 0.138), or clinical stage ( P = 0.453). The correlation of the hypermethylation pattern and the presence of its expression on the tumors, evaluated by immunohistochemistry, is also discussed. Conclusion: We were able to observe an elevated rate of DCC promoter hypermethylation in HNSCC (by Q-MSP) and its absence on saliva DNA from normal subjects. Its presence was also associated with consumption of alcohol in the HNSCC population. Significance: The high rate of DCC promoter hypermethylation has significant implications for the use and evaluation of DCC promoter hypermethylation in the progression and detection of HNSCC. Support: None reported.