
<ArticleTitle>Clinicopathological significance of vascular endothelial growth factor <prot>(<prot>VEGF</prot>)-C</prot> in human esophageal squamous cell carcinomas.</ArticleTitle>
<AbstractText>The purpose of this study was to investigate the expression of vascular endothelial growth factor <prot>(<prot>VEGF</prot>)-C</prot> in human esophageal squamous cell carcinomas to elucidate its role in lymph node metastasis and tumor progression. The expression of <prot>VEGF-C</prot> and <prot>flt-4</prot> 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 <prot>CD34</prot> (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 <prot>VEGF-C</prot> mRNA. In 8 (66.7%) of 12 cases, <prot>VEGF-C</prot> mRNA was detected in only tumor tissues but not in normal mucosa by RT-PCR. There was a significant relationship between <prot>VEGF-C</prot> and <prot>flt-4</prot> mRNA expression. Out of the 48 surgical specimens of esophageal carcinomas, 19 (39.6%) and 10 (20.8%) exhibited intense <prot>VEGF-C</prot> immunoreactivity in the cytoplasm of many cancer cells and the stromal cells, respectively. In contrast, <prot>Flt-4</prot> was mainly expressed on the lymphatic endothelial cells. Normal and dysplastic esophageal squamous epithelium exhibited no or faint cytoplasmic staining of <prot>VEGF-C</prot>. <prot>VEGF-C</prot> expression correlated with depth of tumor invasion, tumor stage, venous invasion, lymphatic invasion and lymph node metastasis. Vessel count was significantly higher in the <prot>VEGF-C</prot> positive tumors than in the negative tumors. These results overall suggest that <prot>VEGF-C</prot> may play a role in tumor progression via lymphangiogenesis and angiogenesis in human esophageal carcinoma.</AbstractText>
