Promoter hypermethylation and quantitative expression analysis of CDKN2A (p14ARF and p16INK4a) gene in esophageal squamous cell carcinoma

Shuhei Ito, Takefumi Ohga, Hiroshi Saeki, Masayuki Watanabe, Yoshihiro Kakeji, Masaru Morita, Tomomi Yamada, Yoshihiko Maehara

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18 Citations (Scopus)


Background: Abnormal hypermethylation of the CDKN2A (p14ARF and p16INK4a) gene can lead to repression of gene expression and contribute to carcinogenesis and tumor progression. Materials and Methods: In esophageal squamous cell carcinoma (ESCC), the promoter methylation of the p14ARF and p16INK4a gene was investigated in 38 cases by methylation-specific PCR and the expression of each gene in 18 cases was quantified by real-time quantitative reverse transcription-PCR. Results: Aberrant methylation of p14ARF and of p16INK4a was detected in 23 (61%) and 29 (76%) cases, respectively. No relationship was found between clinicopathological variables and p14ARF or p16 INK4a promoter methylation. A statistically significant association between p14ARF methylation status and mRNA expression was found (p=0.0441). Regarding p14ARF, a low expression group showed a significantly higher proportion of cases with deep invasion of tumor, lymph node metastasis, and a high TNM stage of disease (p=0.0474, 0.0474, and 0.0441, respectively), and a significantly poor prognosis (p=0.0402). Regarding p16 INK4a, no relationship was found among the methylation status, mRNA expression and clinicopathological variables, including survival. Conclusion: Our results suggest that methylation is the predominant mechanism of inactivation of the p14ARF gene in ESCC. The decrease in p14 ARF gene expression associated with invasive and metastatic phenotypes may be significant as an indicator of the malignant potential of human ESCC.

Original languageEnglish
Pages (from-to)3345-3353
Number of pages9
JournalAnticancer research
Issue number5 A
Publication statusPublished - Sep 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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