Abstract
8522 Background: Angiogenesis is an essential process in the development and growth of tumors. There are a large number of angiogenic mediators including the angiopoietin (Ang) family which acts in association with the vascular endothelial growth factor system to control vessel assembly during tumor progression. Therefore, these factors have been suggested as diagnostic and in some studies as prognostic tumor markers. The purpose of the present study was to evaluate the potential role of circulating soluble Ang-1 and 2 in metastatic malignant melanoma patients and their usefulness as markers in this pathology. Methods: Using a sensitive enzyme-linked immunosorbent assays, circulating Ang-1 and Ang-2 levels were measured in the sera of 67 patients with histologically proven stage IV metastatic melanoma treated by biochemotherapy; 23 had regional lymph node metastasis and 44 patients had distant organ metastasis. Results: Serum Ang-2 levels were significantly elevated in patients compared to controls (median 4,856 vs. 2,225 pg/mL, p < 0.001), there was no significant difference in Ang-1 levels, while the ratio of Ang-2/Ang-1 was significantly elevated in patients compared to controls (0.13 vs. 0.066, p < 0.001). Circulating Ang-1 level was higher in men than in women (p = 0.031). Patient's age, Breslow's classifications or LDH levels were not associated with serum angiopoetin levels. Serum Ang-2 levels were significantly elevated in patients with distant metastases compared with those without metastasis (median 5,080 vs. 3,360 pg/mL, p = 0.01). Tumour burden i.e. number of metastatic sites were not statistically significantly associated with Ang-2 levels. But, only patients with lymph node metastases (n = 23) had significantly lower levels than the 44 patients withmetastases at other sites (mean 3,250 vs. 4,458 pg/mL, p = 0.028). Time to disease progression was worse in patients with elevated Ang-2 levels (p = 0.04). Conclusions: Serum Ang-2 but not Ang-1 is elevated in metastatic malignant melanoma patients. Ang-2 may be a useful serum marker for monitoring of melanoma patients. In addition, it may be a promising therapeutic target for melanoma. No significant financial relationships to disclose.
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