Hypermethylation of RUNX3 but not WIF1 gene and its association with stage and nodal status of tongue cancers

Abstract

Recent studies indicate various molecular abnormalities in oral squamous cell carcinomas (OSCC), including DNA methylation of tumor-associated genes. Although promoter hypermethylation of Wnt pathway antagonists RUNX3 (Runt-related transcription factor 3) and Wnt inhibitory factor 1 (WIF1) has been identified as a common event in a number of carcinomas, methylation status and the role of RUNX3 as a possible tumor suppressor in oral and head and neck cancer are yet controversial. The aim of our study is to determine the occurrence of RUNX3 and WIF1 genes hypermethylation and correlation with tumor and host-related factors and prognosis in tongue carcinomas. Material and Methods: In 76 patients with tongue carcinoma, RUNX3 and WIF1 genes promoter hypermethylation analysis was assessed by nested methylation-specific PCR method. Results: Hypermethylation of WIF1 and RUNX3 genes promoters was observed in 35% and 25% of carcinomas, respectively. RUNX3 gene promoter hypermethylation was significantly associated with lymph node involvement (P=0.013) and tumor stage (P=0.006), but not with the overall survival. Occurrence of RUNX3 and WIF1 genes comethylation was associated with nodal status (P= 0.058) and tumor stage (P=0.055). Conclusions: Our findings indicate that RUNX3 and WIF1 are frequently aberrantly methylated and that RUNX3 promoter methylation could be considered as a potential prognostic marker in tongue carcinoma. © 2011 John Wiley & Sons A/S.