[The expression of p53, p16, cyclin D1 in esophageal squamous cell carcinoma and esophageal dysplasia]

Korean J Gastroenterol. 2006 Oct;48(4):269-76.
[Article in Ko]

Abstract

Backgrounds/aims: p53 is known to play a central role in sensing and signaling for the growth arrest and apoptosis in cells with DNA damage. Mutation of p53 is a frequent event in esophageal squamous cell carcinoma (ESCC). p16 protein binds to cyclin dependent kinase 4 (CDK4) inhibiting the ability of CDK4 to interact with cyclin D1, and stimulates the passage through the G1 phase of cell cycle. We observed the expression patterns and frequencies of p53, p16, and cyclin D1 in esophageal dysplasia and in esophageal squamous cell carcinomas.

Methods: In 15 patients of ESCC, 5 patients of esophageal dysplasia and 5 volunteers with normal esophagus, tissue specimens were taken from esophageal lesions during the operation or endoscopic examination. We used specific monoclonal antibodies for p53 protein, p16(INK4 ) protein and cyclin D1. Immunoreactivity was scored.

Results: Mean age of all groups was 66 years old (range 47-93) and men to women ratio was 19:1. p53 mutation was observed in 87% (13/15) of ESCC, in 80% (4/5) of esophageal dysplasia, in 0% (0/5) of normal mucosa (p=0.001). p16 expression was seen in 40% (2/5) of esophageal dysplasia, 27% (4/15) of ESCC and 100% (5/5) of normal mucosa (p=0.016). Cyclin D1 expression was not significantly different among 20% (1/5) of esophageal dysplasia, 53% (8/15) of ESCC and 20% (1/5) of normal mucosa. Either the expression of p53 mutation or the loss of p16 occurred in 80% (4/5) of esophageal dysplasia and in 93% (14/15) of ESCC.

Conclusions: The expression of p53 mutation and the loss of p16 might play a central role in the pathogenesis of esophageal squamous cell carcinoma (ESCC), and contribute to the development of precancerous lesion such as dysplasia. In addition, there is a possibility that the mutations of p53 and p16 silencing would be the early events in ESCC development.

Publication types

  • Comparative Study
  • English Abstract

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cyclin D1 / immunology
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p16 / immunology
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophagus / abnormalities*
  • Esophagus / metabolism
  • Esophagus / pathology
  • Female
  • G1 Phase
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Tumor Suppressor Protein p53 / immunology
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • Tumor Suppressor Protein p53
  • Cyclin D1