Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas

Int J Cancer. 2001 Sep 1;93(5):662-6. doi: 10.1002/ijc.1379.


The purpose of this study was to investigate the expression of vascular endothelial growth factor (VEGF) -C in human esophageal squamous cell carcinomas to elucidate its role in lymph node metastasis and tumor progression. The expression of VEGF-C and flt-4 genes was examined in 5 esophageal carcinoma cell lines, 12 fresh biopsy specimens and 48 archival surgical specimens of human esophageal carcinoma tissues by RT-PCR and immunohistochemistry. Immunohistochemistry using antibodies against CD34 (endothelial cell specific) was also carried out and microvessels were quantified by counting vessels in a 200x field in the most vascular area of the tumor. Of the 5 human esophageal carcinoma cell lines, 4 constitutively expressed VEGF-C mRNA. In 8 (66.7%) of 12 cases, VEGF-C mRNA was detected in only tumor tissues but not in normal mucosa by RT-PCR. There was a significant relationship between VEGF-C and flt-4 mRNA expression. Out of the 48 surgical specimens of esophageal carcinomas, 19 (39.6%) and 10 (20.8%) exhibited intense VEGF-C immunoreactivity in the cytoplasm of many cancer cells and the stromal cells, respectively. In contrast, Flt-4 was mainly expressed on the lymphatic endothelial cells. Normal and dysplastic esophageal squamous epithelium exhibited no or faint cytoplasmic staining of VEGF-C. VEGF-C expression correlated with depth of tumor invasion, tumor stage, venous invasion, lymphatic invasion and lymph node metastasis. Vessel count was significantly higher in the VEGF-C positive tumors than in the negative tumors. These results overall suggest that VEGF-C may play a role in tumor progression via lymphangiogenesis and angiogenesis in human esophageal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Endothelial Growth Factors / metabolism*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Prognosis
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Growth Factor / metabolism
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor Receptor-3


  • Endothelial Growth Factors
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor C
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-3