title: Infantile hemangiomas are arrested in an early developmental vascular differentiation state.
abstract: Infantile hemangiomas, the most common tumors of infancy, are vascular tumors characterized by rapid proliferation of endothelial cells during the first few months of postnatal life followed by slow spontaneous involution, whose molecular pathogenesis remains unclear. The recent identification of developmental expression of vascular lineage-specific markers prompted us to characterize infantile hemangiomas for the expression of lymphatic endothelial hyaluronan receptor-1 (LYVE-1), Prox-1, CD31 and CD34. We found that LYVE-1, a specific marker for normal and tumor-associated lymphatic vessels, was strongly expressed in tumor cells of infantile hemangiomas (n=28), but not in other vascular tumors including pyogenic granulomas (n=19, P<0.0001) or intramuscular hemangiomas (n=9), using LYVE-1/CD31 double immunostains. Whereas LYVE-1 expression was detected on the endothelial cells of all proliferating infantile hemangiomas, this lymphatic marker was absent from the lesional capillaries during involution in the majority of cases (P=0.0009). The majority of LYVE-1(+) endothelial cells also expressed CD34, but were negative for the lymphatic-specific homeobox protein Prox-1. Based on coexpression of both LYVE-1 and the blood vascular marker CD34, we propose that the endothelial cells in proliferating infantile hemangioma are arrested in an early developmental stage of vascular differentiation. The immature, incompletely differentiated immunophenotype of proliferating infantile hemangiomas may contribute to their rapid growth during the first few months of life.
authors.affiliation: Cutaneous Biology Research Center and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. sam.dadras@cbrc2.mgh.harvard.edu
authors.forename: Soheil S
authors.initials: SS
authors.lastname: Dadras
authors.forename: Paula E
authors.initials: PE
authors.lastname: North
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bertoncini
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006023:Glycoproteins / Q000032:analysis; D006391:Hemangioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D019043:Vascular Neoplasms / Q000378:metabolism / Q000473:pathology*; D033921:Vesicular Transport Proteins
chemical_list: D018952:Antigens, CD34; D006023:Glycoproteins; C119248:LYVE1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D033921:Vesicular Transport Proteins