Vascular Endothelial Growth Factor is a Useful Predictor of Postoperative Distant Metastasis and Survival Prognosis in Esophageal Squamous Cell Carcinoma

Abstract

Background: The correlation between vascular endothelial growth factor (VEGF) and prognosis for patients with esophageal squamous cell carcinoma (ESCC) is controversial. This study investigated the correlation of VEGF expression with distant metastases and prognosis in resectable ESCC to improve the identification of patients with increased risk of postoperative metastases.

Methods: Data from two centers were used to establish a training cohort (n = 319) and a validation cohort (n = 164). Tissue microarrays were generated for immunohistochemical evaluation. The correlations among VEGF expression, clinicopathologic variables, and prognosis were analyzed. The outcomes generated from the training cohort then were tested using the validation cohort. Multivariate analyses were used to test the independent factors that had an impact on postoperative distant metastases, overall survival (OS), and distant metastasis-free survival (DMFS).

Results: Tumor stages, tumor cell grade, and VEGF expression were prognostic factors independent of ESCC outcome. The data indicated that high levels of VEGF expression were correlated with a high risk of postoperative distant metastases (p = 0.013) in the training cohort. This result was confirmed by the validation cohort (p < 0.01) and logistic regression analyses. A high level of VEGF expression also was correlated with poor DMFS (p = 0.011) and OS (p = 0.033) in the training cohort, which also was confirmed by the validation cohort and Cox regression analyses.

Conclusions: Expression of VEGF is a predictor of distant metastasis, OS, and DMFS in resectable ESCC patients. Using a combination of VEGF expression, tumor stages, and tumor cell grade, identification of patients with increased risk of postoperative metastases may become possible.