Xue Hou1,2,3, Jin-Chang Wei4, Jian-Hua Fu2,3,5,6, Xin Wang5, Rong-Zhen Luo7, Jie-Hua He7, Lan-Jun Zhang5, Peng Lin5, Hao-Xian Yang8,9,10,11. 1. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. 2. State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China. 3. Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, People's Republic of China. 4. Department of Thoracic Surgery, Linzhou Esophageal Cancer Hospital, Linzhou, Henan, People's Republic of China. 5. Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. 6. Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, People's Republic of China. 7. Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. 8. State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China. yanghx@sysucc.org.cn. 9. Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, People's Republic of China. yanghx@sysucc.org.cn. 10. Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. yanghx@sysucc.org.cn. 11. Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, People's Republic of China. yanghx@sysucc.org.cn.
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.
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.