Differentiation of Cell Lines in Oral Hemangiomas by Surface Markers

The classification of hemangiomas and vascular malformations by Mulliken and Glowacki 1982, based on endothelial characterization, resulted in a systematized and standardized description and assessment of vascular lesions. The next step based on this classification, the development of a causal and differentiated therapy, has not been accomplished, as the various treatment protocols still applied show. The increased knowledge about endothelial changes, angiogenesis, anti-angiogenesis and hematopoiesis allows a more specific insight into the development. Nowadays it has been assumed that embryologic development of both hematopoietic and endothelial cell lines are based on the same progenitor cell, the hemangioblast, and that differentiation starts at that point. The aim of this retrospective study was to analyze the distribution of hematopoietic and endothelial cells and progenitor cells of oral hemangiomas in a collective of children, and to conclude the formation and maturation of the lesions. The specimens of 20 oral hemangiomas (12 cavernous and 8 capillary) were analyzed. The age of the children at the time of excision was one to eight years. The formalin-fixed and paraffin-embedded specimens were stained immunohistochemically for specific surface cell markers. Proliferation activity was demonstrated by using MIB-1. Antibodies used for this study were CD 31, FLK-1/KDR and VE-Cadherin as markers for endothelial cells, and CD 34, CD 45 and TER 119 as markers for hematopoietic cells. The staining activity was determined by semiquantitative analysis of five at random chosen hot spots of each lesion. The results showed MIB-1+ staining in all cases demonstrating proliferation activity and excluding resting embryologic malformations. The analysis of cell specific constellations of markers showed 47% angioblasts (CD 31+, FLK-1/KDR+, VE-Cadherin+), 30% hemangioblasts (CD 31+, FLK-1/KDR+, VE-Cadherin+, CD 34+, CD 45-), 9% hematopoeitic progenitor cells (FLK-1/KDR+, CD 45+, VE-Cadherin-), 1% non-defined cell line; 13% could not be assigned to one of this groups. The capillary group showed more hematopoietic progenitor cells than the cavernous group. Overall, the endothelial cells seem to be dominant over the hematopoietic cells in oral hemangiomas in infancy. Therefore an intralesional local antiangiogenic therapy in cases of growing and unoperable hemangiomas is conceivable. Keywords: hemangioma, cell lines, immunohistochemistry, differentiation