Hypoxia and apoptosis are core findings of Spitz morphology of combined melanocytic nevi
journal contributionposted on 28.03.2018, 18:54 by Salvador J. Diaz-Cano, Fatima Al-Hashimi, Lucia Pozo-Garcia
Background: The microvessel profile bases in cutaneous melanocytic lesions are poorly understood, in particular for combined Spitz tumors (CST). No study has correlated microvessel profile and HIF1α expression with cell kinetics by topographic and phenotypic compartments in CST to date. Design: We selected combined Spitz tumorconventional melanocytic nevi (44), and malignant melanomas (43, 23 radial growth phase MMRGP and 20 vertical growth phase MMVGP), the latter two groups used as controls. Immunostaining for Ki67 and HIF1α, and in situ end labeling (ISEL) of DNA fragments (using Klenow fragment of DNA polymerase I) were scored by topographic (junctional, dermal above 0.76 mm, and dermal below 0.76 mm) and phenotypic (conventional, ST) compartments, screening the whole compartment in each case. Appropriate controls were run in each sample. CD31stained slides were used to estimate microvessel density. The results were statistically compared using analysis of variance and Student ttest, and considered significant if P<0.05. Results: Superficialtodeep gradient was maintained for Ki67 in all lesions, but was significantly higher in MM. From junctional to deep dermal compartments, ST showed a progressive and statistically significant increase of ISEL indices (5.39%, 5.84%, 9.48%), a microvessel density (4.38, 4.39, 7.41 vessels/HPF), and no correlation between them. The Ki67/ISEL index increased in MM but keeping a superficialdeep gradient in MMRGP only. Conclusion: Localized ischemic changes drive ST morphology of combined nevi (deep dermal upregulation of HIF1α directly correlated with apoptosis), in contrast to the apoptosis independent HIF1 upregulation of vertical growth phase MM. This overexpression represents an additional mechanism of relatively inefficient neovascularization, which does not correlate directly with the vascular density level.