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. 2018 Oct 19;13(1):181.
doi: 10.1186/s13023-018-0928-x.

Estrogen is involved in hemangioma regression associated with mast cells

Fang Hou  1   2   3 , Yuemeng Dai  3 , Chun-Yang Fan  4 , James Y Suen  5 , Gresham T Richter  6   7
Affiliations

Estrogen is involved in hemangioma regression associated with mast cells

Fang Hou et al. Orphanet J Rare Dis. .

Abstract

Background: 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. In addition, the unexpected relationship between mast cells (MCs) and estrogen in human IH was discussed.

Methods: IH (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.

Results: ER-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.

Conclusions: E2 and ER-a are expressed on MCs and not on IH endothelial cells. Furthermore, activated MCs may be involved in IH regression.

Keywords: Estradiol; Estrogen receptor; Infantile hemangioma; Mast cells.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of the University of Arkansas for Medical Sciences.

Informed consent has obtained from 29 patients.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Immunostaining for Glut-1, E2, tryptase and ER-a in IH. a All IH specimens were positive for GLUT-1, which was localized in the cytoplasm of IH endothelial cells (IHC, × 100). Large numbers of tryptase (b), ER-a (c), and E2 (d) positive cells were observed in all IH specimens, specifically in the cytoplasm and nucleus of MCs, but not in IH endothelial cells (IHC, × 400)
Fig. 2
Fig. 2
Immunostaining for E2 and tryptase in IH. Large numbers of E2 (a, IHC, × 100; b and c, IHC, × 200) and tryptase (d, IHC, × 100; E and F, IHC, × 200) positive MCs were found within all IH specimens. IH in the proliferative phase (a, b, d, and e) contained fewer E2 and tryptase positive MCs compared with early involuting phase specimens (c and f) (IHC, × 200)
Fig. 3
Fig. 3
Dual staining for E2 (green, A) and tryptase (red, B) of IH sections. a, b Multiple cells (white arrowheads) showed strong immunoreactivity for E2 (a) and tryptase (b) (IHC, × 200). c Cell nuclei were counterstained with DAPI (blue, C) (IHC, × 200). d Merged image showing multiple MCs (white arrowheads) dually stained for E2 and tryptase (IHC, × 200)
Fig. 4
Fig. 4
Positive MCC in IH: General patterns of positive MCC in different phases of IH (mean±SD).
See this image and copyright information in PMC

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