Impact of VEGF and VEGF receptor 1 (FLT1) expression on the prognosis of stage III esophageal cancer patients after radiochemotherapy

Abstract

Background and purpose: High expression of vascular endothelial growth factor (VEGF) is negatively associated with clinical outcome. The prognostic value of VEGF receptor 1 (FLT1) is unclear. This retrospective study investigated the impact of tumor expression of VEGF and FLT1 on outcome in 68 stage III esophageal cancer patients.

Material and methods: The impact of tumor VEGF and FLT expression (< or =10% vs. > 10%) and five additional potential prognostic factors on overaLL survival (OS) and Locoregional control (LC) was retrospectively evaluated. These factors included T-stage (T3 vs. T4), N-stage (NO vs. N1), treatment (radiochemotherapy plus resection vs. radiochemotherapy alone), erythropoietin (ERYPO 10000, Janssen-Cilag, Neuss, Germany) administration during radiotherapy, and majority of hemoglobin levels during radiotherapy (<12 vs. > or =12 g/dl). Subgroup analyses were performed for patients receiving resection (R0 vs. R1/2 resection). The factors found to be significant on univariate analyses (Kaplan-Meier method, log-rank test) were included in multivariate analyses performed with the Cox proportional hazard model.

Results: On univariate analysis, improved OS was associated with T3 stage (p = 0.011), surgery (p = 0.019), and hemoglobin > or =12 g/dl (p < 0.001). Improved LC was associated with T3 stage (p = 0.025), hemoglobin > or =12 g/dl (p < 0.001), and VEGF negativity (p = 0.045). On multivariate analyses, only hemoglobin maintained significance. In patients having surgery, RO resection was significantly better than R1/2 resection for OS (p < 0.001) and LC (p < 0.001).

Conclusion: Preradiotherapy tumor VEGF expression appears negatively correlated with outcomes, whereas FLT1 expression appears to have no significant impact on OS and LC.