Abstract:
Objective This work aims to investigate the expressions of vascular endothelial growth factor-c(VEGF-C), stromal cell-derived factor-1(SDF-1), and human chemokine(C-X-C motif) receptor 4(CXCR4) in esophageal squamous cell carcinoma.In addition, their correlation with clinicopathological factors and their effect on the prognostic value are also investigated.
Methods The immunohistochemical expressions of VEGF-C, SDF-1, and CXCR4, the relationship among them, and the clinicopathological factors including nodal metastasis and prognostic value in the surgical specimens from 95 patients with primary esophageal squamous cell carcinoma were assayed.
Results VEGF-C, SDF-1, and CXCR4 proteins were mainly located in the cytoplasm of the tumor cells.The positive expression rates of VEGF-C, SDF-1, and CXCR4 were 89.5%, 84.2%, and 69.5%, respectively.The positive expressions of VEGF-C and SDF-1 were significantly correlated with the cellular differentiation degree, tumor invasion depth, nodal metastasis, number of nodal metastasis, and the tumor, node, and metastasis(TNM) stage as defined by the World Health Organization.The positive rates of VEGF-C and SDF-1 expressions were higher in patients with lymph node metastasis than in those without lymph node.Significant differences were observed between the two(χ2=6.319, P=0.012;χ2=5.821, P=0.016).However, the positive expression of the CXCR4 protein was only correlated with the cellular differentiation degree.The Kaplan-Meier survival analysis results show the tumor invasion depth, lymph node metastasis, number of the metastasized lymph nodes, pathological TNM(pTNM) stage, and the expressions of VEGF-C, SDF-1, and CXCR4.The multivariate analysis results show that the tumor invasion depth, nodal metastasis, number of metastatic lymph nodes, pTNM stage, and expression of SDF-1 were independent prognostic factors.
Conclusion The expressions of VEGF-C and SDF-1 proteins exhibit a correlation with the clinicopathological variables, especially the lymph node metastasis.Evaluating the SDF-1 expression is useful to determine tumor characteristics, such as nodal metastasis and prognosis, in patients with esophageal squamous cell carcinoma.Moreover, VEGF-C and SDF-1/CXCR4 proteins may have a synergistic effect on the lymph node metastasis of esophageal squamous cell carcinoma.