β-Adrenergic receptor expression in vascular tumors

• Published in: Modern pathology Vol. 25; no. 11; pp. 1446 - 1451
• Main Authors: Chisholm, Karen M, Chang, Kay W, Truong, Mai T, Kwok, Shirley, West, Rob B, Heerema-McKenney, Amy E
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2012
• Subjects: 631/208/199; 631/67/1059; 692/699/67; Biomarkers, Tumor - analysis; Cell Proliferation; Hemangioendothelioma - chemistry; Hemangioendothelioma - pathology; Hemangioma - chemistry; Hemangioma - pathology; Hemangiosarcoma - chemistry; Hemangiosarcoma - pathology; Humans; Immunohistochemistry; Laboratory Medicine; Medicine; Medicine & Public Health; Neoplasms, Vascular Tissue - chemistry; Neoplasms, Vascular Tissue - pathology; original-article; Pathology; Phosphorylation; Receptors, Adrenergic, beta-2 - analysis; Receptors, Adrenergic, beta-3 - analysis; Tissue Array Analysis; adrenergic; immunohistochemistry; infantile hemangiomas; tissue microarray; vascular
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.2012.108

Propranolol has recently emerged as an effective therapy for infantile hemangiomas causing regression. The β -adrenergic receptor (AR) antagonist is thought to cause vasoconstriction by its effect on nitric oxide, block angiogenesis by its effect on vascular endothelial growth factor (VEGF), and induce apoptosis. In a prior report, we identified expression of β 2-AR (B2-AR) and its phosphorylated form (B2-ARP) in a case of infantile hemangioma that responded to propranolol treatment. We now explore the expression of β ARs on a variety of vascular lesions utilizing a tissue microarray containing 141 lesions, including infantile hemangiomas, angiosarcomas, hemangiomas, hemangioendotheliomas, and various vascular malformations. The array was immunostained for B2-AR, B2-ARP, and β 3-AR (B3-AR), and the results scored for the intensity of endothelial cell expression as negative, weak positive, or strong positive. All phases of infantile hemangiomas had strong expression of all three receptors, with the exception of only weak expression of B2-ARP in the proliferative phase infantile hemangioma. Strong expression of all three receptors was present in many hemangiomas, hemangioendotheliomas, and vascular malformations. Absent to weak expression of all three receptors was seen in glomus tumor, hobnail hemangioendothelioma, pyogenic granuloma, and reactive vascular proliferations. This is the first study to report β -AR expression in a variety of vascular lesions. Although immunohistochemical expression of the receptors does not necessarily indicate that similar pathways of responsiveness to β -blockade are present, it does raises the possibility that β -blockade could potentially affect apoptosis and decrease responsiveness to VEGF. Additional study is warranted, as therapeutic options are limited for some patients with these lesions.