Patterns of neural differentiation in melanomas

Abstract

BackgroundMelanomas, highly malignant tumors arise from the melanocytes which originate as multipotent neural crest cells during neural tube genesis. The purpose of this study is to assess the pattern of neural differentiation in relation to angiogenesis in VGP melanomas using the tumor as a three dimensional system.MethodsTumor-vascular complexes [TVC] are formed at the tumor-stroma interphase, by tumor cells ensheathing angiogenic vessels to proliferate into a mantle of 5 to 6 layers [L1 to L5] forming a perivascular mantle zone [PMZ]. The pattern of neural differentiation is assessed by immunopositivity for HMB45, GFAP, NFP and synaptophysin has been compared in: [a] the general tumor [b] tumor-vascular complexes and [c] perimantle zone [PC] on serial frozen and paraffin sections. Statistical Analysis: ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures [Tukey Test].ResultsThe cells abutting on the basement membrane acquire GFAP positivity and extend processes. New layers of tumor cells show a transition between L2 to L3 followed by NFP and Syn positivity in L4&L5. The level of GFAP+vity in L1&L2 directly proportionate to the percentage of NFP/Syn+vity in L4&L5, on comparing pigmented PMZ with poorly pigmented PMZ. Tumor cells in the perimantle zone show high NFP [65%] and Syn [35.4%] positivity with very low GFAP [6.9%] correlating with the positivity in the outer layers.DiscussionFrom this study it is seen that melanoma cells revert to the embryonic pattern of differentiation, with radial glial like cells [GFAP+ve] which further differentiate into neuronal positive cells [NFP&Syn+ve] during angiogenic tumor-vascular interaction, as seen during neurogenesis, to populate the tumor substance.

Hormone Expression in Melanomas Related to Tumor Angiogenesis

“…The above findings correlate with expression of neural markers as well as biogenic amines in the TVCs [29,30,31] .…”

Tumor Vascular Interaction in Melanomas and Neurogenesis: A Review

“…The above findings correlate with expression of neural markers as well as biogenic amines in the TVCs [12,21,66]. PRL/HGH positivity associated with mitosis, coincides with the appearance of indoleamines, the presence of melatonin indicating the effect of biophoton emissions during mitosis.…”

“…The present work has been undertaken to investigate whether a similar interaction occurs in melanomas in response to angiogenesis. This study is a sequel to a recent finding that melanoma cells revert to the embryonic pattern of differentiation, with radial glial like cells and neuronal positive cells during tumor-vascular interaction [12]. A combined reticulin gold impregnation is employed to identify glial cells [21].…”

“…In Vertical Growth Phase (VGP) melanomas there is a definite pattern of neural differentiation in relation to angiogenesis on viewing the tumor as a three dimensional system [12]. Although most human cancers persist in situ for months in a prevascular phase, they require efficient vascularisation, for further growth and metastasis [13].…”

Melanocyte-endothelial melanomas: Plasticity and transdifferentiation in melanomas

“…Transient TVCs are formed by the interaction of angiogenic vessels with tumor cells at the interphase between the tumor stroma, with a perivascular mantle zone (PMZ) consisting of 5 to 6 cell layers (see Figure 4B, a-c). [15] The periluminal cells, continuous with the endothelial tubes, show nestin positivity, aurophilia (93%), and GFAP positivity (91.5%) to form the innermost layer of the TVC. [16] Nes positivity is seen in 94.5% of cells in the LI layer around the lumen.…”