The Changes of Angiogenesis and Immune Regulations in Stromal Microenvironment of Cutaneous Melanomas.

Tumour microenvironment contributes to growth and metastasis, where angiogenesis and immune alteration suppressing its effectory function belong to main factors. Our study is focused on an analysis of microvascular density (MVD), quantification of FOXP3+ T regulatory lymphocytes (Tregs) and PD-L1 lymphocytes, which are associated with a tumour-cells immune escape mechanism. We examined 95 cutaneous melanomas devided in four groups according to TNM classification - pT1 (35), pT2 (21), pT3 (21), pT4 (18) and 25 melanocytic nevi as a control group. Investigated parameters were detected on paraffin embedded tissues by indirect immunohistochemistry, and evaluated by light microscope in central (C) and at peripheral regions (P) on a 1mm2 „hot spot“ region (the area of the highest density). We found a significant MVD increase correlating with a stage of disease, mostly at the edge of tumours (p=0,0001). Lymphocytic PD-L1 expresion was increased in melanomas of pT3 and pT4 stages, also predominantly at the periphery of lesions (p=0,0001). Numbers of FOXP3 lymphocytes positively correlated with a melanoma stage, where higher values were observed in central areas (p=0,008). Our study documents that stimulation of angiogenesis and induction of an adaptive immune response correlate with a melanoma stage. The most prominent changes are at the tumour periphery confirming heterogeneity of a tumour stroma, which is more prominent in advanced tumours, and which may contribute to higher agresivity of these stages.