PEDIATRICS Vol. 105 No. 1 January 2000, pp. 117-120
EXPERIENCE AND REASON:
Steroid Therapy of a Proliferating Hemangioma: Histochemical and
Molecular Changes
Received Jan 19, 1999; accepted May 4, 1999.
,
* Department of Medicine, Wellington School of Medicine
Swee Tan Plastic Surgery Trust
§ Malaghan Institute of Medical Research
Wellington, New Zealand
Objectives. Hemangioma is a primary tumor of the microvasculature in which angiogenesis is initially excessive, followed by regression of the newly formed vessels. Intervention is necessary in up to 20% of cases, high-dose systemic or intralesional steroids being the first-line treatment. As the mechanism of action of steroids is unknown, we undertook an investigation of the 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 ulcerated proliferating hemangioma before and after intralesional triamcinolone injection, which resulted in an accelerated regression of the lesion. Histochemical quantitation of mast cells, molecular analysis by reverse transcriptase-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
= 2.22 ± .27 [standard error of the mean {SEM}]; treated
= 8.7 ± .71 [SEM] mast cells per field, respectively;
P < .0001; n = 40 fields for each group), and
the transcriptional expression of cytokines: platelet-derived growth
factor-A and -B; interleukin-6; transforming growth factor-
1 and
-
3 decreased, while that of basic fibroblast growth
factor (bFGF) and vascular endothelial cell growth
factor remained unaltered. Elevated urinary bFGF levels noted in cases of proliferating hemangioma, 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 therapy was accompanied by a significant increase in mast cell density, reduced transcription of several cytokines, and an enhanced expression of the mitochondrial cytochrome b gene. Key words: hemangioma therapy, angiogenesis, cytokines, differential display, cytochrome b.
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