CpG Island Hypermethylation in Gastric Carcinoma and Its Clinicopathological Implication
SY Park, MC Kook, YW Kim, NY Cho, GH Kang. National Cancer Center, Goyang-si, Korea; Seoul National University College of Medicine, Seoul, Korea
Background: Gastric carcinoma is one of the human cancers in which promoter CpG island hypermethylation is frequently found. EBV-positive gastric cancer and microsatellite instability-positive gastric carcinoma are well known to harbor frequent promoter CpG island hypermethylation. However, in gastric carcinomas negative for microsatellite instability and EBV, clinicopathological features associated with CpG island hypermethylation remain unclear.
Design: We analyzed 196 cases of gastric carcinoma for their methylation status in 16 cancer-specific methylation markers using MethyLight assay and correlated their methylation with clinicopathological features.
Results: The number of genes methylated was 14.4, 10.3, and 6.2 for EBV-positive gastric cancer (n=16), microsatellite instability-positive gastric cancer (n=30), and EBV-negative/ microsatellite instability-negative gastric cancer (n=150), respectively (P<0.001). With exclusion of EBV-positive or microsatellite instability-positive gastric cancers from the analysis, higher number of methylated genes was found in gastric cancers of female patients than in those of male patients (7.4 vs. 5.6, P=0.004), in infiltrative gross types (Borrman III or IV) than in fungating types (I or II) (6.4 vs. 4.8, P=0.051), in high grade differentiation than in low grade differentiation (6.7 vs. 4.4, P=0.001), in high stage (III or IV) than in low stage (I or II) (6.7 vs. 5.3, P=0.016). Mixed-type, diffuse-type, and intestinal-type gastric cancers were in a decreasing order of the number of methylated genes (9.2, 6.9, and 4.8; P<0.001). Hypermethylation at 14 markers or more was closely associated with poor clinical outcome and found to be an independent prognostic factor.
Conclusions: The findings indicate a close relationship of frequent CpG island hypermethylation with specific clinicopathological features and suggest that aberrant CpG island hypermethylation might be involved in the genesis of mixed-type gastric cancer.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 63, Tuesday Afternoon