mRNA Expression of Vascular Endothelial Growth Factor-C and -D in Esophageal Squamous Cell Carcinoma

Lymph node metastasis is a major prognostic factor for esophageal cancer patients. However, the molecular mechanisms underlying node metastasis remain unclear. Vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor-D (VEGF-D), which are ligands for VEGFR-3, have been reported to be capable of stimulating lymphangiogenesis under in vivo experimental conditions. The aim of the present study was to measure VEGF-C and/or VEGF-D mRNA expression in clinical specimens of esophageal squamous cell carcinoma, and to examine the correlation between VEGF-C or VEGF-D messenger ribonucleic acid (mRNA) expression and conventional clinicopathological parameters, especially the lymphatic involvement of esophageal squamous cell carcinoma. As a previous study has demonstrated that an expression pattern of high VEGF-C and low VEGF-D is correlated with both lymph node metastasis and lymphatic invasion of cancer cells, we also investigated the VEGF-C/D ratio. Total RNAs were isolated from 51 surgical specimens of esophageal carcinoma tissue and 42 normal esophageal mucosae. The relative mRNA abundance of VEGF-C and VEGF-D was measured by real-time quantitative reverse transcription polymerase chain reaction (PCR) analysis, and mRNA expression of VEGF-C and VEGF-D was standardized against glceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression. VEGF-C mRNA was expressed similarly in esophageal carcinoma tissue and normal mucosal tissue ; however, VEGF-D mRNA expression was significantly lower in carcinoma tissue compared with normal mucosal tissue, and therefore the VEGF-C/VEGF-D ratio was significantly increased in tumors compared with normal mucosae. However, neither mRNA expression of VEGF-C or VEGF-D nor the VEGF-C/VEGF-D ratio correlated with any clinicopathological factors, including lymphatic invasion, venous invasion, lymph node status, and tumor stage. VEGF-C and VEGF-D gene expression do not appear to be involved in the lymphatic progression of esophageal carcinoma.