Receptor of ghrelin is expressed in cutaneous neurofibromas of individuals with neurofibromatosis 1

Abstract

BackgroundMultiple 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.ResultsSample 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-R-positive cells and intensity of GHS-R expression were positively correlated with neurofibromas volume. GHS-R expression was more common in female gender.ConclusionsGHS-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.Electronic supplementary materialThe online version of this article (10.1186/s13023-017-0734-x) contains supplementary material, which is available to authorized users.

Prevalence and clinicopathological characteristics of lipomatous neurofibromas in neurofibromatosis 1: An investigation of 229 cutaneous neurofibromas and a systematic review of the literature

“…For the S100 and leptin immunohistochemistry investigation, larger lesions, three to five morphologically representative cores (1.1 mm diameter) were included in tissue microarray blocks constructed as previously described . For small lesions, whole specimens were evaluated after inclusion in tissue macroarrays, which were constructed as described previously . For CD34 antibody, the whole specimens were investigated.…”

Ghrelin Represses Thymic Stromal Lymphopoietin Gene Expression through Activation of Glucocorticoid Receptor and Protein Kinase C Delta in Inflamed Skin Keratinocytes

“…GHSR1a is highly expressed in the hypothalamus and pituitary, but it is weakly expressed in the pancreas, spleen, kidney, and adrenal gland [ 83 , 84 , 85 ]. Although it has been previously reported that GHSR1a is not detected in mouse and human skin by quantitative RT-PCR [ 84 , 85 ], immunohistochemical examination demonstrated that GHSR1a was present in skin epidermis and annexes surrounding neurofibromas [ 86 ]. In skin wounds, granulation tissues are positive for GHSR1a in the dermis [ 34 ].…”

Attribution of Ghrelin to Cancer; Attempts to Unravel an Apparent Controversy

“…No significant correlations were found between ghrelin and GHS-R1a expression (88). Likewise, tumor GHSR expression was associated with higher tumor size in patients with neurofibromatosis 1 (89). Like RCC, this is another example of dominance of in-vitro local findings in the summary clinical role of ghrelin in a type of human cancer.…”