Receptor of ghrelin is expressed in cutaneous neurofibromas of individuals with neurofibromatosis 1
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LETTER TO THE EDITOR
Open Access
Receptor of ghrelin is expressed in cutaneous neurofibromas of individuals with neurofibromatosis 1 Rafaela E. Rozza-de-Menezes1,2,3, Nicolle C. Gaglionone1, Raquel M. Andrade-Losso1,2, Orlando H. K. Siqueira4, Lilian M. Almeida1,2, Kamila da S. Peruzini5, Marco A. C. Guimarães-Filho4, Carolina I. Brum6, Mauro Geller7,8 and Karin S. Cunha1,2,6*
Abstract Background: Multiple cutaneous neurofibromas are a hallmark of neurofibromatosis 1 (NF1). They begin to appear during puberty and increase in number and volume during pregnancy, suggesting a hormonal influence. Ghrelin is a hormone that acts via growth hormone secretagogue receptor (GHS-R), which is overexpressed in many neoplasms and is involved in tumorigenesis. We aimed to investigate GHS-R expression in NF1 cutaneous neurofibromas and its relationship with tumors volume, and patient’s age and gender. Results: Sample comprised 108 cutaneous neurofibromas (55 large and 53 small tumors) from 55 NF1 individuals. GHS-R expression was investigated by immunohistochemistry in tissue micro and macroarrays and quantified using a digital computer-assisted method. All neurofibromas expressed GHS-R, with a percentage of positive cells ranging from 4.9% to 76.1%. Large neurofibromas expressed more GHS-R than the small ones. The percentage of GHS-Rpositive cells and intensity of GHS-R expression were positively correlated with neurofibromas volume. GHS-R expression was more common in female gender. Conclusions: GHS-R is expressed in cutaneous neurofibromas. Larger neurofibromas have a higher percentage of positive cells and higher GHS-R intensity. Based on our results we speculate that ghrelin may have an action on the tumorigenesis of cutaneous neurofibromas. Future studies are required to understand the role of ghrelin in the pathogenesis of NF1-associated cutaneous neurofibroma. Keywords: Neurofibromatosis 1, Neurofibroma, Ghrelin, Ghrelin receptor
Background Multiple cutaneous neurofibromas (cNfs) are a hallmark of neurofibromatosis 1 (NF1). They begin to appear during puberty and increase in number and volume during pregnancy [1–3], suggesting a hormonal influence. Most neurofibromas express progesterone and androgen receptors [4, 5] and in vitro and in vivo studies have shown that neurofibromas grow in the presence of sex hormones [6–8]. * Correspondence: [email protected] 1 Graduate Program in Pathology, School of Medicine, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Av. Marquês do Paraná, 303, 4o andar, sala 01 – Centro, Niterói, RJ 24033-900, Brazil 2 Neurofibromatosis National Center (Centro Nacional de Neurofibromatose), Rio de Janeiro, RJ, Brazil Full list of author information is available at the end of the article
Beyond sex hormones, it is possible that other hormones, such as components of growth hormone (GH) axis, could have a role in the pathogenesis of NF1associated neurofibromas. Most NF1 neurofibromas express GH receptors, which suggests that GH exerts a direct effect on these neoplasms [
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