Lymphatic vessel density and VEGF-C expression as independent predictors of melanoma metastases

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In many patients, the clinical behaviour of cutaneous melanoma is very difficult to predict by traditional histologic and clinical parameters. This study aimed to examine the role of quantitative parameters of tumour lymphangiogenesis and vascular endothelial growth factor (VEGF)-C in predicting metastatic risk in patients with cutaneous melanoma. One hundred melanoma specimens were stained with lymphatic-specific antibody D2-40 and with anti-VEGF-C antibody. Quantitative parameters of lymphangiogenesis-lymphatic vessel density (LVD) and lymphatic vessel area (LVA)-were determined by computer-assisted morphometric analysis. Moderate or strong staining was assessed as a positive expression of VEGF-C in tumour cells. Univariate analysis revealed that intratumoural LVD, peritumoural LVD, VEGF-C expression in tumour cells, melanoma thickness, Clark level, ulceration, gender and histologic type were significant predictors of lymph node metastasis (p=0.000, p=0.000, p=0.000, p=0.000, p=0.005, p=0.005, p=0.011 and p=0.027, respectively). No significant association of intratumoural and peritumoural LVA with metastases was found. In multivariate analysis, independent predictors of metastatic risks were melanoma thickness [odds ratio OR=1.655, 95% confidence interval (CI) 1.102-2.484, p=0.015], intratumoural LVD (OR=1.086, 95% CI 1.027-1.148, p=0.004), peritumoural LVD (OR=1.050, 95% CI 1.008-1.094, p=0.020) and a positive VEGF-C expression in tumour cells (OR=20.337, 95% CI 2.579-160.350, p=0.004). This study identified intratumoural and peritumoural LVD and the VEGF-C expression in tumour cells as more significant predictors of metastatic risk than melanoma thickness, ulceration and other clinical-pathological parameters.