CpG island methylator phenotype of cell-cycle regulators associated with TNM stage and poor prognosis in patients with oesophageal squamous cell carcinoma

Aims CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation, and the cell-cycle regulatory proteins often change in human neoplasms. To gain insight into the role of epigenetic aberration of cell-cycle regulator genes in oesophagus squamous cell carcinoma (ESCC), the authors determined the hypermethylation profile in ESCC. Methods The promoter methylation status of nine cell-cycle regulator genes was examined in 50 ESCC, 50 dysplastic tissues and 50 normal epithelial tissues by methylation-specific PCR. Results The frequency of promoter methylation was 52% for p14, 44% for p15, 50% for p16, 56% for p21, 38% for p27, 8% for p53, 42% for p57, 36% for p73, and 44% for RB1 of 50 ESCC. CIMP+ was detected in 54% (27/50) of ESCC and 8% (4/50) of dysplastic tissues; no CIMP+ was present in normal epithelial tissues (p<0.001). The results show that promoter methylation of p14, p15, p16, p21, p27, p57 and p73 was far more common in ESCC samples with CIMP+ than those with CIMP-. A significant difference between CIMP status and TNM stage and metastasis was found in ESCC (p<0.05). Patients with ESCC with CIMP+ had poorer 4-year survival than those with CIMP-. Conclusions The results suggest that CIMP of a subset of cell-cycle regulatory genes has an important role in the pathogenesis and progression of ESCC.