Steroid therapy of a proliferating hemangioma: Histochemical and molecularchanges

Objectives. Hemangioma is a primary tumor of the microvasculature in which angiogenesis is initially excessive, followed by regression of the newly fo rmed vessels. Intervention is necessary in up to 20% of cases, high-dose sy stemic or intralesional steroids being the first-line treatment. As the mec hanism of action of steroids is unknown, we undertook an investigation of t he cellular and molecular effects of their action. Study Design. A unique opportunity to study the effect of steroid treatment was presented when biopsy material was obtained from an infant with an ulc erated proliferating hemangioma before and after intralesional triamcinolon e injection, which resulted in an accelerated regression of the lesion. His tochemical quantitation of mast cells, molecular analysis by reverse transc riptase-polymerase chain reaction (RT-PCR) for 7 growth factor transcripts and differential display RT-PCR (DD RT-PCR) were conducted. Results. After steroid therapy, the mast cell number increased (untreated ( x) over bar = 2.22 +/- .27 [standard error of the mean {SEM}]; treated (x) over bar = 8.7 +/- .71 [SEM] mast cells per field, respectively; P <.0001; n = 40 fields for each group), and the transcriptional expression of cytoki nes: platelet-derived growth factor-A and -B; interleukin-6; transforming g rowth factor-beta 1 and -beta 3 decreased, while that of basic fibroblast g rowth factor (bFGF) and vascular endothelial cell growth factor remained un altered. Elevated urinary bFGF levels noted in cases of proliferating heman gioma, persisted even after steroid treatment. Using DD RT-PCR an amplicon that shared 100% sequence homology with the human mitochondrial cytochrome b gene was detected in the hemangioma biopsy after steroid treatment. Conclusions. The regression of this hemangioma subsequent to steroid therap y was accompanied by a significant increase in mast cell density, reduced t ranscription of several cytokines, and an enhanced expression of the mitoch ondrial cytochrome b gene.