In this review, Pandiani et al. discuss the differences in tumorigenic processes (etiologic factors and genetic alterations) and tumor biology (gene expression and signaling pathways) between cutaneous melanoma and uveal melanoma.,Cutaneous melanoma (CM) and uveal melanoma (UM) derive from cutaneous and uveal melanocytes that share the same embryonic origin and display the same cellular function.,However, the etiopathogenesis and biological behaviors of these melanomas are very different.,CM and UM display distinct landscapes of genetic alterations and show different metastatic routes and tropisms.,Hence, therapeutic improvements achieved in the last few years for the treatment of CM have failed to ameliorate the clinical outcomes of patients with UM.,The scope of this review is to discuss the differences in tumorigenic processes (etiologic factors and genetic alterations) and tumor biology (gene expression and signaling pathways) between CM and UM.,We develop hypotheses to explain these differences, which might provide important clues for research avenues and the identification of actionable vulnerabilities suitable for the development of new therapeutic strategies for metastatic UM.
CTCs provide prognostic information and their application is under investigation in multiple tumor types.,Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source.,To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients.,Blood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements.,CTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8).,Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p = 0.003).,There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases.,Our data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells.,Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs.,•CTCs were detectable in 100% of arterial blood obtained from metastatic uveal melanoma patients, while only 53% of venous blood was positive for CTCs.,CTCs were detectable in 100% of arterial blood obtained from metastatic uveal melanoma patients, while only 53% of venous blood was positive for CTCs.,CTCs have been investigated to provide prognostic information in multiple tumor types.,Of the multiple variables, none is more important than the appropriateness of the sample source.,Blood specimens were obtained from both femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases.,CTCs were detectable with greater frequency (100%) and in larger numbers in all arterial blood specimens than in venous samples (52.9%).,Our data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells.,Although less convenient, arterial blood should be evaluated as sample source for measurement of CTCs.