VEGF as a biomarker for metastatic uveal melanoma in humans

Purpose: High levels of serum VEGF have been reported in many types of cancers, especially in the metastatic stage. The aim of this study was to examine the potential of VEGF serum level as a tumor marker for metastases in uveal melanoma (UM) patients. Materials and Methods: Levels of serum VEGF were analyzed by ELISA for 23 UM patients (none of whom developed metastases within 5 years from diagnosis) at the time of diagnosis, soon after treatment, and 3 years later, and compared with serum VEGF levels of 39 metastatic patients, 58 10-year disease-free (10yDF) patients, and 23 healthy subjects. VEGF ratios were calculated per patient between diagnosis and after treatment, and between diagnosis and 3 years later. Matched pairs univariate analysis was performed for 17 metastatic patients for whom sera were available from before and after the diagnosis of metastases. Patients were followed biannually with liver ultrasonography and liver function tests for the presence of metastases. Results: The inter-patient VEGF level range was large (e.g., the range for the metastatic patients was 46-1892 pg/ml). The mean ± SD levels for the control, 10yDF, and metastatic groups were: 329.65±190.0, 407.66±261.9 and 453.52±270.2, respectively (p=0.2456). The mean VEGF level ratio from after treatment to diagnosis was 1.08 (p=0. 0024), and the ratio from 3 years after diagnosis to diagnosis was 1.53 (p=0.0009). The mean ± SE post/premetastatic levels ratio was 1.35±0.21 (p=0.0595). Conclusions: Serum VEGF increased significantly after metastases developed. However, the wide inter-patient variance precludes the use of any cut-off level to determine the metastatic status of an individual patient based on a single VEGF serum level. An increase in VEGF on serial measurements may indicate the development of metastases. Further investigation is warranted to assess VEGF's value as a predictive marker for metastatic disease.