Recurrence in oral and pharyngeal cancer is associated with quantitative MGMT promoter methylation

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Abstract
Background: Biomarkers that predict clinical response, tumor recurrence or patient survival are severely lacking for most cancers, particularly for oral and pharyngeal cancer. This study examines whether gene-promoter methylation of tumor DNA correlates with survival and recurrence rates in a population of patients with oral or pharyngeal cancer.Methods: The promoter methylation status of the DNA repair geneMGMTand the tumor suppressor genesCDKN2A and RASSF1were evaluated by methylation-specific PCR in 88 primary oral and pharyngeal tumors and correlated with survival and tumor recurrence. QuantitativeMGMTmethylation was also assessed.Results: 29.6% of the tumors presented withMGMTmethylation, 11.5% withCDKN2Amethylation and 12.1% withRASSF1methylation.MGMTpromoter methylation was significantly associated with poorer overall and disease-free survival. No differences in methylation status ofMGMTandRASSF1with HPV infection, smoking or drinking habits were observed. A significant inverse trend with the amount ofMGMTmethylation and overall and disease-free survival was observed (ptrend= 0.002 and 0.001 respectively).Conclusion: These results implicateMGMTpromoter methylation as a possible biomarker for oral and pharyngeal cancer prognosis. The critical role of MGMT in DNA repair suggests that defective DNA repair may be correlative in the observed association betweenMGMTpromoter methylation and tumor recurrence. Follow-up studies should include further quantitative MSP-PCR measurement, global methylation profiling and detailed analysis of downstream DNA repair genes regulated by promoter methylation.

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