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.
Razon
M J
MJ
Surgical Research Laboratory, Children's Hospital, Boston, MA 02115, USA.
Kräling
B M
BM
Mulliken
J B
JB
Bischoff
J
J
D000367:Age Factors; D017209:Apoptosis; D016022:Case-Control Studies; D002455:Cell Division; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000254:growth & development / Q000473:pathology; D006391:Hemangioma / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009365:Neoplasm Regression, Spontaneous / Q000473:pathology; D009389:Neovascularization, Pathologic; D012867:Skin / Q000166:cytology; D012878:Skin Neoplasms / Q000473:pathology*