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 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.
Kitadai
Y
Y
Department of Endoscopy, Hiroshima University School of Medicine, Hiroshima, Japan. ykitadai@mcai.med.hiroshima-u.ac.jp
Amioka
T
T
Haruma
K
K
Tanaka
S
S
Yoshihara
M
M
Sumii
K
K
Matsutani
N
N
Yasui
W
W
Chayama
K
K
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3
D016228:Endothelial Growth Factors; D017978:Receptors, Growth Factor; D042582:Vascular Endothelial Growth Factor C; D020794:Receptor Protein-Tyrosine Kinases; D040321:Vascular Endothelial Growth Factor Receptor-3