Background: Epigenetic silencing of tumor-related genes by CpG island methylation is an important mechanism for the development of many tumors, including gastric carcinoma. Deregulation of transcription factor 4 (TCF4) by promoter methylation was recently shown to play a key role in gastric carcinogenesis.
Methods: The extent of methylation in the TCF4 promoter was assessed using methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PS) in 120 gastric carcinoma (GC) samples collected during gastrectomy, and in 40 normal gastric mucosa samples.
Results: The PS analysis of GCs revealed a higher frequency of TCF4 methylation (75.8%; 91/120). The methylation frequency for TCF4 by both MSP and PS techniques was significantly higher in advanced (75.0 and 91.7%, respectively) compared with early (60.0 and 60.0%, respectively, p < 0.05) GCs. There was a significant difference in TCF4 methylation between GCs and normal gastric mucosa (67.5 vs. 40.0%, respectively, by MSP and 75.8 vs. 30.0%, respectively, by PS; p < 0.05). There was significant correlation between TCF4 methylation status by PS and tumor size (p = 0.004), Lauren classification (p = 0.043), depth of invasion (p < 0.001), nodal metastasis (p = 0.021), and tumor-node-metastasis (TNM) stage (p = 0.045).
Conclusions: These results suggest that inactivation of TCF4 by promoter methylation may play a role in the early stage of gastric carcinoma progression. Furthermore, standard polymerase chain reaction followed by PS may provide a more specific and quantitative diagnostic alternative to MSP, which may be of benefit in oncology research.