Expression pattern of the lymphatic and vascular markers VEGFR-3 and CD31 does not predict regional lymph node metastasis in cutaneous melanoma

Malignant melanoma of the skin preferentially metastasises via the lymphatic system. Novel molecular biomarkers, which are involved in malignant transformation, proliferation, angiogenesis and lymphangiogenesis, are currently under investigation to elucidate the risk for lymph node metastasis. To this end, the vascular endothelial growth factors VEGF-C and VEGF-D have been identified to promote lymphangiogenesis and lymphatic spread through activation of its receptor, Vascular endothelial growth factor receptor-3 (VEGFR-3). Prompted by this assumption, we estimated the degree of lymphangiogenesis by semiquantitative immunohistochemical analysis of the expression of VEGFR-3 and the panvascular marker CD31 in primary cutaneous melanoma (n=26) and correlated these findings with the sentinel lymph node (SLN) status. The cohort was selected for matched prognostic markers in SLN-positive and SLN-negative patients. In contrast to other studies, we observed an inverse correlation between expression of these markers with lymph node metastases. Additionally, no difference between intratumoral versus peritumoral CD31- or VEGFR-3 expression on blood vessels versus lymphatic capillaries could be detected. Interestingly, VEGFR-3 upregulation was not restrained to vascular structures but also appeared on tumor cells. In summary, in our series VEGFR-3/CD31 immunohistochemical staining of primary melanoma does not serve as a valid marker to predict lymph node involvement. As lymphatic spread is a complex, multi-step process, several different biomarkers have to be combined to define new prognostic subgroups in cutaneous melanoma.