Increased apoptosis coincides with onset of involution in infantile hemangioma.

OBJECTIVE: Hemangioma is an endothelial cell tumor that grows rapidly during infancy and regresses slowly during childhood. However, little is known about the natural history of this common tumor. To gain insight into the cellular mechanisms that underlie the switch from uncontrolled growth to involution of endothelium, we investigated the extent of cellular apoptosis versus proliferation in hemangioma specimens that spanned the natural life cycle of the tumor. METHODS: We analyzed apoptosis and cellular proliferation in frozen sections from 16 hemangioma specimens using the TUNEL assay to detect apoptotic cells and the Ki67 antigen to detect dividing cells. RESULTS: Apoptosis was low in proliferative phase hemangiomas but increased fivefold in involutive phase specimens obtained from children one to four years of age. Immunofluorescence double-labeling experiments showed that at least one third of the apoptotic cells were endothelial. As expected, cellular proliferation was high in specimens up to 2 years of age but decreased significantly thereafter. Apoptosis was consistently low in nine normal skin tissues (newborn to 4 years of age) obtained from discarded pathology specimens. CONCLUSIONS: These results suggest that increased apoptosis during the second year of life can offset cellular proliferation and may be involved in initiating regression of hemangioma.

E-selectin is present in proliferating endothelial cells in human hemangiomas.

E-selectin, an endothelial-cell-specific leukocyte adhesion molecule, may also function in angiogenesis. To investigate its role in a noninflammatory angiogenic disease, E-selectin was analyzed by immunohistochemistry in specimens of proliferative phase and involutive phase hemangiomas. Hemangioma is an endothelial cell tumor of capillary blood vessels that grows rapidly during infancy and regresses spontaneously during childhood. E-selectin expression was high in proliferative phase specimens and was co-localized with dividing microvascular endothelial cells. Relative to the number of blood vessels, E-selectin declined significantly in involutive phase specimens demonstrating that E-selectin correlates with angiogenesis in the tumors. E-selectin was not detected in quiescent endothelium but was co-localized in dividing microvascular endothelial cells in placenta and neonatal foreskin, two tissues with ongoing growth of microvessels. These in vivo studies support the hypothesis that E-selectin functions in angiogenesis and suggest that E-selectin may be a marker for proliferating endothelium.