β1-Adrenoceptor mRNA level reveals distinctions between infantile hemangioma and vascular malformations.
BACKGROUND
Infantile hemangioma (IH) is the most frequent vascular tumor of early childhood. Recently, propranolol, a nonselective β1- and β2-adrenoceptor inhibitor, was introduced into the therapy of severe proliferating IH with excellent results. However, the underlying mechanism of action of propranolol is still unclear.


METHODS
We performed immunohistochemistry for cluster of differentiation 31 (CD31), D2-40, glucose transporter-1 (GLUT-1), and Ki67 in order to characterize 21 vascular anomalies (nine IH, seven venous malformations (VMs), and five lymphatic malformations (LMs)). Furthermore, we analyzed the expression of β1-, β2-, and β3-adrenoceptor mRNA in these specimens as well as in hemangioma-derived stem cells by quantitative real-time PCR (qPCR).


RESULTS
We show that the expression of β1-adrenoceptor mRNA is 10.7-fold higher in IH independent of the proliferative or regressive phase as well as 2.5-fold higher in hemangioma-derived stem cells as compared with β2-adrenoceptor mRNA. In LM, the expression of β2-adrenoceptor mRNA was ninefold higher than that of β1-adrenoceptor mRNA. VM showed low expression levels of all β-adrenoceptor mRNAs, and β3-adrenoceptor mRNA was hardly detectable in any specimens examined.


CONCLUSIONS
These results provide the first evidence of distinctions between IH and vascular malformations with regard to β-adrenoceptor subtype mRNA levels.
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Hospital of Freiburg, Freiburg, Germany. jochen.roessler@uniklinik-freiburg.de
Jochen
J
Rössler
Miriam
M
Haubold
Ralf
R
Gilsbach
Eva
E
Jüttner
Daniela
D
Schmitt
Charlotte Marie
CM
Niemeyer
Lutz
L
Hein
D000293:Adolescent; D058846:Antibodies, Monoclonal, Murine-Derived; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005819:Genetic Markers; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D018324:Hemangioma, Capillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D019394:Ki-67 Antigen / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054079:Vascular Malformations / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
C547787:ADRB1 protein, human; C553443:ADRB2 protein, human; C568534:ADRB3 protein, human; D058846:Antibodies, Monoclonal, Murine-Derived; D005819:Genetic Markers; D051272:Glucose Transporter Type 1; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; C495677:SLC2A1 protein, human; C500987:monoclonal antibody D2-40