Expression of p53 protein in esophageal squamous cell carcinoma: relation to hypoxia-inducible factor-1alpha, angiogenesis and apoptosis

Pathobiology. 2005;72(4):179-85. doi: 10.1159/000086787.

Abstract

Objectives: Hypoxia-inducible factor (HIF)-1 is important in the control of transcription of several genes related to angiogenesis. We have previously reported that expression of HIF-1alpha correlates with venous invasion and clinical outcome in esophageal squamous cell carcinoma. p53 has been reported to interact with HIF-1alpha and induce ubiquitin-mediated proteosomal degradation of HIF-1alpha. The purpose of this study was to clarify whether the expression of p53 is associated with that of HIF-1alpha.

Methods: Expression of p53, HIF-1alpha and vascular endothelial growth factor (VEGF) was examined in 81 archival surgical specimens of human esophageal squamous cell carcinoma tissue. CD34 and single-stranded DNA were used to evaluate angiogenesis and apoptosis.

Results: Forty-seven of the 81 (58.0%) tumor specimens showed high levels of nuclear p53 immunoreactivity. Overexpression of p53 was observed in the early clinical stage of tumor development. Expression of p53 was not correlated with HIF-1alpha or VEGF expression, angiogenesis or apoptosis in esophageal carcinoma.

Conclusions: These results suggest that mutations in p53 play a role in carcinogenesis but not in the progression of esophageal squamous cell carcinoma. HIF-1alpha may not only be regulated by p53 but also by other factors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD34 / metabolism
  • Apoptosis*
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Esophageal Neoplasms / blood supply
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunohistochemistry
  • Japan
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / metabolism*
  • Retrospective Studies
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antigens, CD34
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A