CpG island methylator phenotype of cell-cycle regulators associated with TNM stage and poor prognosis in patients with oesophageal squamous cell carcinoma. Issue 3 (17th December 2010)

• Record Type: Journal Article
• Authors: Ling, Yang; Huang, Guoliang; Fan, Lieying; Wei, Lixin; Zhu, Jing; Liu, Yongping; Zhu, Changtai; Zhang, Changsong
• Is Part Of: Journal of clinical pathology. Volume 64:Issue 3(2011)
• Page Start: 246
• Page End: 251
• Publication Date: 2010-12-17
• Subjects: CIMP -- methylation -- cell-cycle gene -- oesophagus squamous cell carcinoma -- molecular oncology -- oncology; Pathology -- Periodicals; Pathology, Molecular -- Periodicals; 616.0705
• DOI: 10.1136/jcp.2010.082875
• Languages: English
• ISSNs: 0021-9746

Abstract

Abstract : 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.