The Expression And Significance Ofβ2-AR、VEGFR-2in Infantile Hemangioma

Hemangiomas are the most common tumors of infancy affecting approximately3%-10%children and occurring mote frequently in females than in males, in a ratio of3-5:1. Caucasian ethnicity, prematurity, low birth weight and advanced maternal age are risk factors.Its characteristic pathological changes are excessive proliferation of endothelial cells of proliferating phase and apoptosis of endothelial cells of involuting phase。According to clinical and histopathology presentation, hemangioma is divided into proliferating phase、involuting phase and involuted phase. The natural history of hemangiomas is characterized by excessive proliferation of endothelial cells of proliferating phase, followed by apoptosis of endothelial cells of involuting phase and next fibrous—fatty tissue replace tumor cells of involuted phase. The pathogenesis of hemangiomas is not well understood so far. It has been pointed out that the development and involution of hemangioma are related to the proliferating status of hemangioma endothelium、excessive proliferation of endothelial cells、high expression levels of various angiogenesis cytokines of proliferating phase and high expression levels of angiogenesis inhibitors involuting phase. In recent years, propranolol was found accidently effective for infantile hemangiomas, but its mechanism remains unclear. Propranolol, a nonselective β-blocker,suggest us that we can study the pathogenesis of hemangioma from the endothelial cells receptor point. So we approach the relationship between β2-AR、 VEGFR-2and infantile hemangioma.ObjectiveTo detect the expression of β2-AR and VEGFR-2in the different stages of infantile hemangiomas,approach the effect and significance of β2-AR and VEGFR-2in the occurrence and development of infantile hemangioma. Provide a theoretical basis and guidance for clinical treatment.MethodsCollect the hemangioma specimens embedded in paraffin and fresh hemangioma tissue, fixed with10%formalin and embedded in paraffin. We classified the specimens according to the Mulliken’s classification standard, including proliferating group (32cases), involuting group (17cases)and involuted group (11cases), normal skin tissues from7cases were chosen as control group. The expression of β2-AR and VEGFR-2was detected by two-step immunohistochemical technique in cases of proliferating hemangiomas, involuting hemangiomas, involuted hemangiomas, and normal skins; the mean optical density Was measured by image analysis system and application SPSS16.0software for statistical analysis.Resultsβ2-AR expression:Positive expression of β2-AR was located in cytoplasm or membrane of tumor cells and nomal skin endepidermis. Strongly positive expression in proliferating phase, positive expression in involuting phase, weakly positive expression in involuted phase and weakly positive or negative expression in normal skin tissues. The differences in three stages had a statistically significance(P<0.05).VEGFR-2expression:Positive expression of β2-AR was located in cytoplasm or membrane of tumor cells and nomal skin endepidermis. Strongly positive expression in proliferating phase, positive expression in involuting phase, weakly positive expression in involuted phase and weakly positive or negative expression in normal skin tissues. The differences in three stages had a statistically significance(P<0.05).ConclusionStrongly positive expression in proliferating phase suggest that β2-AR may play a role in hemangioma endothelial cell proliferation and angiogenesis;Propranolol, a nonselective β-blocker, may affect endothelial cell proliferation and apoptosis by blocking the β2-AR mediated signaling pathways then accelerate the involuting of hemangiomas.Strongly positive expression of VEGFR-2in proliferating phase and weakly positive expression in involuted phase suggest that VEGF may play an important role in the process of endothelial cells proliferation, migration, differentiation and angiogenesis by acting on its targeted receptor VEGFR-2,VEGFR-2is an important step in the signal transduction process; β2-AR and VEGFR-2are related, suggest that the β2-AR may influence the expression of VEGFR-2in hemangioma endothelial cells then to play its role in the development and progression of hemangiomas.