Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis

Abstract

BackgroundThe diagnosis of lymph node metastasis in esophageal cancer by the presence and number of metastatic lymph nodes is an extremely important prognostic factor. In addition, the indication of non-surgical therapy is gaining more attention. Vascular endothelial growth factor C (VEGF-C) is potentially lymphangiogenic and selectively induces hyperplasia of the lymphatic vasculature. In this study, we investigated the expression of VEGF-C and whether it correlated with various clinico-pathologic findings.MethodsKYSE series of esophageal cancer cell lines and 106 patients with primary esophageal squamous cell carcinomas who had undergone radical esophagectomy were analyzed. VEGF-C mRNA expression was determined by quantitative RT-PCR.ResultsHigh expression of VEGF-C was detected in most of the KYSE cell lines, especially KYSE410, yet, in an esophageal normal epithelium cell line, Het-1A, VEGF-C was not detected. In the clinical specimen, the expression of VEGF-C in the cancerous tissue was higher than in the corresponding noncancerous esophageal mucosa (p = 0.026). The expression of VEGF-C was found to be higher in Stage2B-4A tumors than in Stage0-2A tumors (p = 0.049). When the patients were divided into two groups according to their expression levels of VEGF-C (a group of 53 cases with high expression and a group of 53 cases with low expression), the patients with high VEGF-C expression had significantly shorter survival after surgery than the patients with low expression (p = 0.0065). Although univariate analysis showed that high expression of VEGF-C was a statistically significant prognostic factor, this was not shown in multivariate analysis. In the subgroup of patients with Tis and T1 tumors, the expression of VEGF-C was higher in N1 tumors than in N0 tumors (p = 0.029). The survival rate of patients from the high expression group (n = 10) was lower than that in the low expression group (n = 11), and all the patients in the low VEGF-C expression group survived.ConclusionsThe expression of VEGF-C correlates with lymph node metastasis and poor prognosis. In patients with Tis and T1 esophageal tumors, the expression of VEGF-C may be a good diagnostic factor for determining metastasis of the lymph node.