Expression of Cathepsins B, D, and G in Infantile Hemangioma

Effective antihypertensive therapy has made a major contribution to the reductions in the morbidity and mortality of cardiovascular disease that have been achieved since the 1960s. However, blood-pressure control with conventional drugs has not succeeded in reducing cardiovascular disease risks to levels seen in normotensive persons. Drugs that inhibit or antagonize components of the renin-angiotensin-aldosterone system are addressing this deficiency by targeting both blood pressure and related structural and functional abnormalities of the heart and blood vessels, thus preventing target-organ damage and related cardiovascular events.

The aetiology and exact incidence of infantile haemangiomas (IHs) are unknown. Prior studies have noted immunohistochemical and biological characteristics shared by IHs and placental tissue.

Juvenile hemangiomas are common, benign vascular tumors of infancy. These lesions enlarge rapidly through cellular hyperplasia during the first year of life and then involute over several years. Distinctive histopathologic features of hemangiomas diminish during this evolution, and differentiation from vascular malformations becomes increasingly difficult. This distinction has important therapeutic implications, as juvenile hemangiomas differ from malformations in natural history and in potential for recurrence. We report here that high endothelial immunoreactivity for the erythrocyte-type glucose transporter protein GLUT1 is a specific feature of juvenile hemangiomas during all phases of these lesions. In a retrospective study, we found intense endothelial GLUT1 immunoreactivity, involving more than 50% of lesional microvessels, in 97% (139 of 143) of juvenile hemangiomas from patients aged 1 month to 11 years. No endothelial GLUT1 immunoreactivity was found in any of 66 vascular malformations (17 arteriovenous, 33 venous, 11 lymphatic, and 5 port-wine) from patients aged 5 days to 75 years, or in any of 20 pyogenic granulomas or 7 granulation tissue specimens. Abundant Ki-67 positivity in these latter lesions established that GLUT1 expression does not simply reflect mitotically active endothelium. Focal GLUT1 immunoreactivity was found in 3 of 12 angiosarcomas, but not in any of 5 hemangioendotheliomas (epithelioid or infantile kaposiform). These findings establish GLUT1 immunoreactivity as a highly selective and diagnostically useful marker for juvenile hemangiomas. Because high levels of endothelial GLUT1 expression in normal tissue are restricted to microvessels with blood-tissue barrier function, these findings also have implications for the molecular and developmental pathogenic mechanisms of juvenile hemangiomas.