Survival prediction in patients with cutaneous melanoma by tumour lymphangiogenesis

Objectives: Melanoma induces lymphangiogenesis by secreting lymphangiogenic growth factors. The aim of this study was to examine the role of tumour lymphangiogenesis in survival of patients with cutaneous melanoma. Methods: Immunostaining of one hundred melanoma specimens was done with lymphatic-specific antibody D2-40. The quantification of tumour lymphangiogenesis - lymphatic vessel density (LVD) and lymphatic vessel area (LVA) - was calculated by computer-assisted morphometric analysis. Results: High intratumoural LVD, high peritumoural LVD, male gender, greater tumour thickness and Clark level IV/V were significantly associated with shorter disease-free survival (p= 0.001, p= 0.004, p= 0.004, p= 0.000 and p= 0.008, respectively) and melanoma-specific survival (p= 0.002, p= 0.002, p= 0.001, p= 0.000 and p= 0.017, respectively), while the trunk melanoma site was significantly associated only with shorter disease-free survival (p= 0.033). No significant association of LVA with survival was found. At multivariate analysis, peritumoural LVD [hazard ratio (HR) = 2.143, 95% confidence interval (CI) 1.097-4.189, p= 0.026)] and melanoma thickness (HR = 1.276, 95%CI 1.106-1.473, p= 0.001) were independent predictors of disease-free survival, while intratumoural LVD (HR = 3.446, 95%CI 1.465-8.109, p= 0.005), peritumoural LVD (HR = 2.742, 95%CI 1.313-5.725, p= 0.007) and gender (HR = 2.880, 95%CI 1.304-6.362, p= 0.009) were independent predictors of melanoma-specific survival. Conclusion: This study shows that LVD enables better prediction of survival than melanoma thickness and other clinical-pathological parameters. Intratumoural LVD is the most significant predictor of melanoma-specific survival, while only peritumoural LVD has a significant impact on both, a disease-free survival and a melanoma-specific survival.