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M. B. Crosby, H. Yang, W. Gao, H. E. Grossniklaus; Serum VEGF Levels Correlate With Tumor Size, Micrometastases and Location of Micrometastases in a Murine Model of Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3390.
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Uveal melanomas secrete VEGF, which can stimulate tumor blood vessel growth and enhance metastatic potential. The detection of serum VEGF may predict the metastatic potential in patients with uveal melanoma and allow for the early treatment of undetectable micrometastases. We predict that micrometastases most often occur in zone 3 of the hepatic acinus system, which is the most hypoxic region around the central vein, compared to zones 1 and 2.
We analyzed the serum of C57Bl/6 mice inoculated with uveal melanomas at days 4, 7, 14 and 21 post inoculation for VEGF levels by ELISA (R&D Systems). We compared the serum VEGF levels with the number and location of hepatic micrometastases. Additionally, we compared VEGF serum levels and micrometastases with the intraocular tumor size and location.
Serum VEGF levels rose after inoculation of C57Bl/6 mouse eyes with the B16LS9 melanoma cells. Beginning on day 14 there was a statistically significant (p < 0.05) increase in VEGF levels in the serum of mice inoculated with the cells, rising to an average peak level of 37.985 pg/mL at day 21. The number of micrometastases was determined for each mouse and correlated with their averaged and peak VEGF serum levels. Peak serum VEGF levels correlated with the total number of hepatic micrometastases (R2=0.444); and there was moderate correlation of peak VEGF serum levels with zone 3 metastases (R2=0.572). Ocular tumor size did not correlate with serum VEGF levels or number of hepatic micrometastases. In general, ocular tumor location did not correlate with either serum VEGF levels or the number of hepatic micrometastases, but the one instance where the ocular tumor occurred exclusively in the intrachoroidal space yielded the highest peak VEGF levels and number of micrometastases.
These data further indicate that serum VEGF may be a marker for the potential for hepatic micrometastases. Additionally, the location of micrometastases is related to the peak levels of serum VEGF. A more sensitive VEGF assay may allow physicians to follow patients treated for uveal melanoma and assess for micrometastases. VEGF inhibition may be useful as a treatment for micrometastatic uveal melanoma.
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