Abstract
BackgroundEstrogen plays a role in infantile hemangioma (IH) development, but the underlying mechanism remains unclear. This study aimed to assess estrogen and estrogen receptor (ER) localization and expression levels in IH. In addition, the unexpected relationship between mast cells (MCs) and estrogen in human IH was discussed.MethodsIH (n = 29), vascular malformation (VMs, n = 33) and normal skin (n = 15) specimens were assessed. IH was classified into proliferative (n = 9; age, 3.56 ± 1.01 months), early involuting (n = 10; age, 8.90 ± 2.69 months) and late involuting (n = 10; age, 20.10 ± 4.93 months) groups. Estradiol (E2), ER-a, ER-β, and tryptase (MC marker) levels were determined immunohistochemically and/or by double immunofluorescence staining. Quantification and localization of tryptase, ER-a, and E2 were assessed for each specimen.ResultsER-a, E2, and tryptase were expressed in the cytoplasm and nucleus of MCs in IH. The IH specimens showed significantly more tryptase, ER-a, and E2 positive MCs (30.6 ± 12.7, 9.7 ± 5.6, and 19.8 ± 8.7 cells/high-power field [HPF], respectively) compared with VM specimens (9.0 ± 9.8, 1.5 ± 2.4, and 2.5 ± 4.1 cells/HPF, respectively) and normal skin (6.1 ± 8.5, 0.5 ± 1.2, and 1.9 ± 3.4 cells/HPF, respectively). Proliferating IH displayed fewer E2 positive MCs (14.0 6.3 cells/HPF) compared with early (22.3 ± 10.2 cells/HPF, P = 0.023) and late (22.4 ± 6.8 cells/HPF, P = 0.006) involuting specimens. In addition, proliferating IH showed fewer tryptase positive MCs (24.7 ± 10.8 cells/HPF) compared with early involuting specimens (35.7 ± 15.3 cells/HPF, P = 0.043). All IH specimens were ER-a positive and ER-β negative.ConclusionsE2 and ER-a are expressed on MCs and not on IH endothelial cells. Furthermore, activated MCs may be involved in IH regression.
Highlights
Estrogen plays a role in infantile hemangioma (IH) development, but the underlying mechanism remains unclear
E2 and estrogen receptor (ER)-a are expressed on mast cells (MCs) and not on IH endothelial cells
Activated MCs may be involved in IH regression
Summary
Estrogen plays a role in infantile hemangioma (IH) development, but the underlying mechanism remains unclear. This study aimed to assess estrogen and estrogen receptor (ER) localization and expression levels in IH. Infantile hemangioma (IH) is the most common benign tumor of infancy, with an incidence estimated at 4.5%, which is higher in the female, caucasian race and low birth weight infants [1, 2]. The natural history of IH is peculiar. It appears at birth or within the first weeks of life and it undergoes a rapid proliferation phase that lasts until the 12th months of life. Estrogen promotes the proliferation of IH’s vascular endothelial cells synergistically with vascular endothelial growth factor (VEGF) in vitro [8]. Little is known about the presence and mechanisms of estrogen and estrogen receptor (ER) in the pathological process of IH
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