Biogenic amines and tumor-vascular interaction in melanomas

Abstract

Background In nodular melanomas in vertical growth phase, tumor-vascular complexes (TVC), with perivascular mantle zone (PMZ) of 5 to 6 layers (L1-L5) of tumor cells are formed around angiogenic vessels at the tumor-stroma interphase, showing organized neural differentiaton. The present study explores the sequence of biogenic amines positivity in relation to angiogenesis, utilizing the TVC as a 3D model. Methods The sequence of positivity for Nestin (Nes), GFAP, indoleamines: serotonin (SER)/melatonin (MLT), catecholamines: dopamine (DA)/noradrenalin (NA), pigment (Pig); dopa oxidase (DO); and related mitosis in layers of the PMZ (L1-L5) was assessed in 897 developing TVCs using 5 µm serial paraffin and frozen sections. Statistical Analysis: ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures (Tukey Test). Results Nes, GFAP appear in L1/L2, next indoleamines (serotonin/melatonin) in L2/L3 associated with mitosis. DA is positive in L3/L4 coinciding with DO which peaks in L4 with NA, Pig appears in L4/L5. Mitosis in L2/L3 is associated with indoleamine positive cells which remain in L2/L3, with catecholamine positive cells moving into L4/L5 thus establishing a polarity. Conclusion Thus, the angiogenic vessel confers polarity and an embryonal microenvironment in the PMZ, the aggressive melanoma cells functioning as neuronal stem cells to resemble early neurogenesis of bio-aminergic cells.