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

The purpose of this study was to investigate the expression of vascular end othelial growth factor (VEGF) -C in human esophageal squamous cell carcinom as to elucidate its role in lymph node metastasis and tumor progression. Th e expression of VEGF-C and flt-4 genes was examined in 5 esophageal carcino ma 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 specif ic) was also carried out and microvessels were quantified by counting vesse ls in a 200x field in the most vascular area of the tumor. Of the 5 human e sophageal 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 n ot 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 esop hageal carcinomas, 19 (39.6%) and 10 (20.8%) exhibited intense VEGF-C immun oreactivity in the cytoplasm of many cancer cells and the stromal cells, re spectively. In contrast, Flt-4 was mainly expressed on the lymphatic endoth elial cells. Normal and dysplastic esophageal squamous epithelium exhibited no or faint cytoplasmic staining of VEGF-C. VEGF-C expression correlated w ith depth of tumor invasion, tumor stage, venous invasion, lymphatic invasi on and lymph node metastasis. Vessel count was significantly higher in the VEGF-C positive tumors than in the negative tumors. These results overall s uggest that VEGF-C may play a role in tumor progression via lymphangiogenes is and angiogenesis in human esophageal carcinoma. (C) 2001 Wiley-Liss, Inc .