Gene expression profiling of human angiotropic primary melanoma: Selection of 15 differentially expressed genes potentially involved in extravascular migratory metastasis

Background and aim: Angiotropism and extravascular migratory metastasis (EVMM) are an important alternative means of melanoma spread. In EVMM, melanoma cells migrate along the external surfaces of vascular channels to distant sites and demonstrate microscopic angiotropism, i.e. melanoma cells arrayed along the external surfaces of vascular endothelium. Pertinent to EVMM are the origin of melanocytes from the neural crest (NC) and strong analogies of EVMM with NC cell migration. Our aim is to elucidate the molecular mechanisms underlying angiotropism and EVMM. Methods: Frozen primary melanomas, previously utilised for gene expression profiling, were analysed for angiotropism as a differential marker. From the results of this new microarray analysis, we sought to identify genes which were directly relevant to the basic mechanisms underlying EVMM. Results: Among 66 melanomas from patients who developed metastases or remained disease-free at 4 years of follow-up, 26 melanomas were angiotropic while 35 were not, and five were equivocal. The new microarray analysis identified 128 genes differentially expressed in angiotropic versus non-angiotropic melanomas. Among these 128 genes, 15 genes were potentially directly involved in EVMM, based their respective expressions in the NC (seven genes), in other malignant tumours of NC origin (three genes), in cell motility and/or migration (four genes) and in neurotropism (one gene). Conclusion: The detection of these 15 genes provides additional support for the importance of angiotropism and the mechanism of EVMM in melanoma. Ongoing studies on this new profile of 15 genes may potentially identify new targets for controlling melanoma metastasis.