Abstract
The identification of prognostic factors in cutaneous melanoma allows choosing the most effective treatment, especially in group of patients with locoregional disease. Markers related to carcinogenesis and angiogenesis in particular have effect on the course of the disease. The aim of this study was to evaluate clinical utility of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase 1 (TIMP-1), and YKL-40 in serum of melanoma patients at pathological stages I–III. We included 148 adult patients with melanoma. The median follow-up was 40 months. Disease recurrence was observed in 43 patients; 3-year disease-free survival (DFS) rate was 71.7 %; 35 patients died; and the 3-year overall survival (OS) rate was 85 %. Concentrations of VEGF, MMP-2, MMP-9, TIMP-1, and YKL-40 were measured by ELISA kits. VEGF, MMP-9, TIMP-1, and YKL-40 were significantly higher in group of patients than in controls. Increased concentrations of TIMP-1 were related to patient survival, which in the group of lower and increased TIMP-1, disease-free survival amounted to 81 vs. 61 % (p = 0.014) and overall survival −88 vs. 82 % (p = 0.050), respectively. An increased concentration of YKL-40 was observed in 59 % of patients with ulceration and in 26 % of patients without ulceration (p = 0.012). We have found a clinically significant correlation between YKL-40 and MMP-9 (rho = 0.363; p = 0.004) as well as YKL-40 and VEGF (rho = 0.306; p = 0.018). In melanoma patients at stages I–III, the high concentrations of TIMP-1 in serum predicted adverse prognosis. YKL-40 was associated with ulceration of primary tumor, which is a very important prognostic factor.
Highlights
Melanoma is a malignant tumor deriving from neuroectodermal melanocytes, and it is one of the most aggressive cancers in humans
No significant correlations appeared between concentrations of tissue inhibitors of metalloproteinase 1 (TIMP-1), matrix metalloproteinases (MMPs)-9, and vascular endothelial growth factor (VEGF) and clinicopathological parameters
We have evaluated a clinical utility of the concentrations of VEGF, matrix metalloproteinase 2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinases (TIMPs)-1, and YKL-40 in serum of patients with skin melanoma at locoregional disease
Summary
Melanoma is a malignant tumor deriving from neuroectodermal melanocytes, and it is one of the most aggressive cancers in humans. Depending on the clinical stage determined in accordance with the classification of the American Joint Committee on Cancer (AJCC), patients are qualified to prognostic groups and linked to the optimal scheme of treatment. The AJCC classification correctly stratifies patients to the risk groups, there is still 50 % of patients with locoregional stage who recur. It is worth to consider to add other prognostic factors which are, e.g., related to tumor biology. Neoangiogenesis is one of the most important processes of tumor development, and vascular endothelial growth factor (VEGF) is a key factor stimulating endothelial cell proliferation, survival, and migration, as well as leading to the increase in permeability of blood vessels. The process of neoangiogenesis is modulated by the activity of matrix metalloproteinases (MMPs) including MMP-2 and MMP-9, and their tissue
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