Abstract
Common infantile hemangioma appears postnatally, grows rapidly, and regresses slowly. Two types of congenital vascular tumors present fully grown at birth and behave differently from infantile hemangioma. These rare congenital tumors have been designated rapidly involuting congenital hemangioma (RICH) and noninvoluting congenital hemangioma (NICH). RICH and NICH are similar in appearance, location, and size, and have some overlapping histologic features with infantile hemangioma. At a molecular level, neither expresses glucose transporter-1, a diagnostic marker of infantile hemangioma. To gain further insight into the molecular differences and similarities between congenital and common hemangioma, we analyzed expression of insulin-like growth factor-2, known to be highly expressed in infantile hemangioma and VEGF-receptors, by quantitative real-time PCR, in three RICH and five NICH specimens. We show that insulin-like growth factor-2 mRNA was expressed in both RICH and NICH, at a level comparable with that detected in common hemangioma over 4 y of age. In contrast, mRNA levels for membrane-associated fms-like tyrosine-kinase receptor, also known as VEGF receptor-1, were uniformly increased in congenital hemangiomas compared with proliferating or involuting phase common hemangioma. These results provide the first evidence of the molecular distinctions and similarities between congenital and postnatal hemangioma.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- FLT-1:
-
fms-like tyrosine-kinase receptor
- GLUT-1:
-
glucose transporter-1
- HIF-1α:
-
hypoxia-inducible factor-1α
- IGF-2:
-
insulin-like growth factor-2
- KDR:
-
kinase-insert domain receptor
- NRP:
-
neuropilin
- NICH:
-
noninvoluting congenital hemangioma
- RICH:
-
rapidly involuting congenital hemangioma
- VEGF-R:
-
VEGF-receptor
References
Enjolras O, Mulliken JB 1998 Vascular tumors and vascular malformations: new issues. Adv Dermatol 13: 375–423
Boon LM, Enjolras O, Mulliken JB 1996 Congenital hemangioma: evidence of accelerated involution. J Pediatr 128: 329–335
Berenguer B, Mulliken JB, Enjolras O, Boon LM, Wassef M, Josset P, Burrows PE, Perez-Atayde AR, Kozakewich HP 2003 Rapidly involuting congenital hemangioma: clinical and histopathologic features. Pediatr Dev Pathol 6: 495–510
Enjolras O, Mulliken JB, Boon LM, Wassef M, Kozakewich HP, Burrows PE 2001 Noninvoluting congenital hemangioma: a rare cutaneous vascular anomaly. Plast Reconstr Surg 107: 1647–1654
Mulliken JB, Enjolras O 2004 Congenital hemangiomas and infantile hemangioma: missing links. J Am Acad Dermatol 50: 875–882
North PE, Waner M, Mizeracki A, Mihm MC Jr 2000 GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas. Hum Pathol 31: 11–22
Ritter MR, Dorrell MI, Edmonds J, Friedlander SF, Friedlander M 2002 Insulin-like growth factor 2 and potential regulators of hemangioma growth and involution identified by large-scale expression analysis. Proc Natl Acad Sci USA 99: 7455–7460
Yu Y, Wylie-Sears J, Boscolo E, Mulliken JB, Bischoff J 2004 Genomic imprinting of IGF2 is maintained in infantile hemangioma despite its high level of expression. Mol Med 10: 117–123
Chen C, Pore N, Behrooz A, Ismail-Beigi F, Maity A 2001 Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia. J Biol Chem 276: 9519–9525
Feldser D, Agani F, Iyer NV, Pak B, Ferreira G, Semenza GL 1999 Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2. Cancer Res 59: 3915–3918
Maru Y, Yamaguchi S, Shibuya M 1998 Flt-1, a receptor for vascular endothelial growth factor, has transforming and morphogenic potentials. Oncogene 16: 2585–2595
Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M 1998 Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92: 735–745
Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G 2000 Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected]. J Biol Chem 275: 18040–18045
Ginzinger DG 2002 Gene quantification using real-time quantitative PCR: an emerging technology hits the mainstream. Exp Hematol 30: 503–512
Acknowledgements
We thank the following members of the Vascular Biology Program, Children's Hospital Boston: Dr. Juan Melero-Martin for advice, Jill Wylie-Sears for technical assistance, Elke Pravda for confocal microscopic imaging, Dr. Akio Shimizu for NRP-2 primer sequences, and Dr. Carmen Barnes for placental tissue RNA.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the Doug and Diana Berthiaume Tribute Fund, P01 AR048564 (National Institutes of Health), Philippe Foundation Inc, (New York City, and Paris, France), AP-HP grant (Assistance Publique des Hôpitaux de Paris, Paris, France).
Rights and permissions
About this article
Cite this article
Picard, A., Boscolo, E., Khan, Z. et al. IGF-2 and FLT-1/VEGF-R1 mRNA Levels Reveal Distinctions and Similarities Between Congenital and Common Infantile Hemangioma. Pediatr Res 63, 263–267 (2008). https://doi.org/10.1203/PDR.0b013e318163a243
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e318163a243
This article is cited by
-
VEGF receptor-2-specific signaling mediated by VEGF-E induces hemangioma-like lesions in normal and in malignant tissue
Angiogenesis (2016)
-
Does hypoxia play a role in infantile hemangioma?
Archives of Dermatological Research (2016)
-
β-adrenergic receptor antagonists inhibit vasculogenesis of embryonic stem cells by downregulation of nitric oxide generation and interference with VEGF signalling
Cell and Tissue Research (2014)
-
Rapidly involuting congenital haemangioma (RICH) of the liver
Pediatric Radiology (2012)
-
Cyclin D1 gene amplification in proliferating haemangioma
Cell and Tissue Research (2009)
