Background:Port-wine stain (PWS) has been classified not as the hyperplasia of cells,but rather,as an expansion of malformed vessels.However,previous studies have reported upregulated expression of proangiogenic factors in PWS.Several studies have indicated that the pathology exhibits proliferation of numerous endothelial cells in hypertrophic/nodular PWS.This study aimed to determine the expression of vascular epithelial growth factor(VEGF),matrix metalloproteinase-9 (MMP-9),angiopoietin-2 (ANG-2),and basic fibroblast growth factor (bFGF)in hypertrophic PWS.Methods:Immunohistochemistry was used to analyze skin samples from 33 patients with hypertrophic PWS.Expression levels of VEGF,MMP-9,ANG-2,and bFGF in hypertrophic PWS were determined by multiplying the intensity by the percentage of immunoreactive cells.Immunoreactivity scores were classified as follows:negative(0),low (1),moderate (2,3,and 4),or high (6).Results:Based on pathological characteristics,hypertrophic PWS was divided into vascular malformation and pyogenic granuloma (PG) types.VEGF,MMP-9,ANG-2,and bFGF were significantly activated in the blood vessels of PG-type PWS samples compared with their counterparts in blood vessels of vascular malformation-type PWS samples and controls.PG-type hypertrophic PWS,which exhibited proliferation of endothelial cells,showed the strongest activation.Conclusion:The exuberant proliferation of endothelial cells in PG-type hypertrophic PWS may be associated with the regulation of proangiogenic factors during development.These proangiogenic factors that function in the angiogenesis and proliferation of endothelial cells may play an important role in the pathogenesis and progression of PWS.Furthermore,these factors may be dynamic and behave differently in various types of hypertrophic PWS.