Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus

Am J Gastroenterol. 2001 Jun;96(6):1733-40. doi: 10.1111/j.1572-0241.2001.03866.x.


Objective: p53 plays a role in tumor angiogenesis, and vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of the present study was to clarify how expression of p53 protein participates in angiogenesis, and whether the coexpression of VEGF and p53 protein has a significance for angiogenesis and the clinicopathological features in esophageal squamous cell carcinoma (SCC).

Methods: Tissues samples were taken from 60 patients with esophageal SCC after surgery. The expression of VEGF and p53 protein in these SCC was examined immunohistochemically. Microvessel density (MVD) was determined by counting microvessels in tumor sections stained for Factor VIII-related antigen. Ki-67 labeling index (LI) was calculated, based on Ki-67 antigen immunostaining, as a proliferative marker. Apoptotic index (AI) was calculated, based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling, to evaluate apoptosis.

Results: VEGF expression was observed in 58.3%, and p53 protein expression was observed in 61.7% of the 60 patients. VEGF and p53 protein were significantly coexpressed in 26 (43.4%). Histological venous invasion (p < 0.01) and distant metastasis (p < 0.05) were significantly correlated with p53 protein expression. The two parameters were more frequently observed in the SCC with VEGF/p53 coexpression than in those without the coexpression. The MVD and Ki-67 LI were significantly higher (p < 0.01 and p < 0.001), and the AI was significantly lower (p < 0.001) in the SCC with p53 protein expression than in the SCC without it. The MVD and Ki-67 LI were higher, and the AI was lower in the SCC with VEGF/p53 coexpression than in those without the coexpression. The 5-yr survival rate in patients with the coexpression was poorer than in the other patients.

Conclusion: These results suggest that mutant p53 expression is associated with angiogenesis and distant metastasis in esophageal SCC, and that the coexpression of p53 and VEGF may play an important role in angiogenesis, and have important clinical significance.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Capillaries / pathology
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism
  • Endothelial Growth Factors / immunology
  • Endothelial Growth Factors / metabolism*
  • Esophageal Neoplasms / blood supply
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Neoplasms / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Lymphokines / immunology
  • Lymphokines / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neovascularization, Pathologic*
  • Survival Rate
  • Tumor Suppressor Protein p53 / immunology
  • Tumor Suppressor Protein p53 / metabolism*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Biomarkers, Tumor
  • Endothelial Growth Factors
  • Ki-67 Antigen
  • Lymphokines
  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors