title: CpG island methylator phenotype of cell-cycle regulators associated with TNM stage and poor prognosis in patients with oesophageal squamous cell carcinoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Clinical Oncology Laboratory, Changzhou Tumor Hospital, Medical College of Suzhou University, Changzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ling
authors.forename: Guoliang
authors.initials: G
authors.lastname: Huang
authors.forename: Lieying
authors.initials: L
authors.lastname: Fan
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Liu
authors.forename: Changtai
authors.initials: C
authors.lastname: Zhu
authors.forename: Changsong
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D018797:Cell Cycle Proteins / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D044127:Epigenesis, Genetic; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D011379:Prognosis
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm