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V. Barak, S. Frenkel, I. Kalickman, J. Pe'er; VEGF as a New Marker for Metastatic Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):875.
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VEGF has been shown both in various in vitro and in vivo models to be mitogenic, chemotactic and instrumental in angiogenic processes. High levels of serum VEGF have been reported in many types of Cancer patients, especially in their metastatic stages. The aim of this study was to examine the potential of VEGF serum levels to provide significance as a Tumor Marker in Uveal Melanoma (UM) patients: to assess differences in VEGF levels between patients after initial treatment, and in their pre metastatic disease free (DF) clinical status, as compared to their metastatic stage and identify earlier liver metastases.
Levels of serum VEGF were analyzed by ELISA for 23 UM patients at the time of diagnosis, close 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 normal controls. None of the 23 study patients developed metastases within 5 years from diagnosis. VEGF ratios were calculated per patient between after treatment and diagnosis, and between diagnosis and 3 years later. Matched pairs univariate analysis was performed for 21 metastatic patients for whom sera were available from before and after the diagnosis of metastases. Patients were followed biannually with liver ultrasonography and blood test for the presence of metastases.
The mean (SE) VEGF level ratio from after treatment to diagnosis was 1.08 (0.07) (p= 0.4050), and the 3-years after diagnosis to diagnosis VEGF level ratio was 1.53 (0.11) (p=0.0014). The inter-patient range was large and can be appreciated from the mean (SD) levels for the control, 10yDF, and metastatic groups (329.65 (190.0), 407.66 (261.9) and 453.52 (270.2), respectively, p=0.2456). The mean (SE) post/pre-metastatic levels ratio was 1.35 (0.21) (p=0.0365).
Serum VEGF levels increased significantly after the development of metastases. However, the wide inter-patient variance makes it difficult 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. The 35% increase in VEGF after development of metastases raises suspicion that the 53% increase 3 years from diagnosis indicated the existence of micrometastases in some of the patients that for unknown reasons did not develop to a full-blown metastatic disease. Further investigation is warranted to assess VEGF’s value as a predictive marker for metastatic disease.
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