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Expression of Follicle-Stimulating Hormone Receptor in Vascular Anomalies
Reid A. Maclellan, MD, MMSc, Matthew P. Vivero, BA, Patricia Purcell, PhD, Harry P. Kozakewich, MD, Amy D. DiVasta, MD, MMSc, John B. Mulliken, MD, Steven J. Fishman, MD, Arin K. Greene, MD, MMSc.
Boston Children's Hospital / Harvard Medical School, Boston, MA, USA.
Introduction: The mechanism for the growth of infantile hemangioma and vascular malformations is unknown. Follicle-stimulating hormone secretion mirrors the life-cycle of infantile hemangioma, and increases during adolescence when vascular malformations often progress. The purpose of this study was to determine if vascular anomalies express the receptor for follicle-stimulating hormone.
Methods: Human vascular tumors (infantile hemangioma, congenital hemangioma, kaposiform hemangioendothelioma, pyogenic granuloma) and vascular malformations (capillary, lymphatic, venous, arteriovenous) were subjected to immunofluorescence for follicle-stimulating hormone receptor. Tissues were co-stained with DAPI and CD31 antibodies to identify nuclei and blood vessels, respectively. Control specimens included normal skin/subcutis, mucosa, liver, spleen, Crohn disease, granulation, pancreatitis, rheumatoid arthritis, and synovitis. Receptor expression and microvessel density were quantified using imaging software.
Results: Follicle-stimulating hormone receptor was expressed in the endothelium of all vascular anomalies, but was not present in control specimens (Figure 1). Receptor staining was greater in proliferating infantile hemangioma (6.0%) compared to the other vascular tumors [congenital hemangioma (0.61%), kaposiform hemangioendothelioma (0.55%), pyogenic granuloma (0.56%)] (p<0.0001), despite similar microvessel density (p=0.1). Follicle-stimulating hormone receptor expression in arteriovenous malformations (2.65%) was elevated compared to the other types of vascular malformations [capillary (1.02%), lymphatic (0.38%), venous (0.76%), (p<0.0001)].
Conclusions: Vascular anomalies express follicle-stimulating hormone receptor on their endothelium, in contrast to vascular control tissues. Vascular anomalies are the only benign, pathological tissue known
to express this receptor. Because the secretion of follicle-stimulating hormone correlates with the growth pattern of infantile hemangioma and vascular malformations, follicle-stimulating hormone might be involved in the pathogenesis of these lesions.
Figure 1: Follicle-stimulating hormone receptor expression in vascular anomalies and control specimens. (A) Proliferating infantile hemangioma (3 months of age). (B) Involuting infantile hemangioma (2 years of age). (C) Involuted infantile hemangioma (10 years of age). (D) Capillary malformation. (E) Lymphatic malformation. (F) Venous malformation. (G) Arteriovenous malformation. (H) Ovary. (I) Skin. Follicle-stimulating hormone receptor (red), blood vessels (green), nuclei (blue).
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