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Vitamin D receptor expression and serum 25(OH)D concentration inversely associates with burden of neurofibromas

Kluwe, Lana,b; Hagel, Christianc; Friedrich, Reinhard E.b; Schnabel, Claudiad; Schön, Gerharde; Mautner, Victora

European Journal of Cancer Prevention: May 2019 - Volume 28 - Issue 3 - p 220–224
doi: 10.1097/CEJ.0000000000000467
Research Papers: Childhood Cancer
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Vitamin D and its receptor may play a role in preventing tumor development and progression. As such antineoplastic effects are expected to be weak and to act over long periods, conditions with increased tumor incidence, such as the neurofibromatosis type 1 (NF1), provide suitable study models. We previously found an inverse correlation of serum 25(OH)D concentration with number of neurofibromas in NF1. Here we aim to further explore the role of the vitamin D receptor. A total of 141 adult NF1 patients were included in the study. For 101 of them, serum vitamin 25(OH)D data were available. From 87 patients, blood samples were obtained in PaxGene tubes containing a reagent to stabilize RNA immediately. mRNA of the vitamin D receptor (VDR) gene (coding for the vitamin D receptor) was measured by means of RT-PCR. Correlation of laboratory data with NF1-related tumors was statistically evaluated. Vitamin D receptor in NF1-tumors was examined by means of immunohistochemistry using an antibody against the vitamin D1 receptor. The number of dermal neurofibromas was significantly inversely correlated with VDR mRNA level and with serum 25(OH)D concentration in NF1 patients. In contrast, plexiform neurofibroma and malignant peripheral nerve sheath tumor did not correlate with these two parameters. Immunostaining did not detect vitamin D receptor in NF1-tumors. Both vitamin D and its receptor may play a role in suppressing the development of neurofibromas. Sustaining 25(OH)D at an adequate level may contribute to controlling neurofibromas and possibly also other tumors. This is especially important for individuals with lower expression of VDR.

aDepartment of Neurology

bDepartment of Maxillofacial Surgery

cInstitute of Neuropathology

dInstitute of Clinical Chemistry

eInstitute of Medical Biometry and Epidemiology, University Medical Center Eppendorf, Hamburg, Germany

Correspondence to Lan Kluwe, PhD, Laboratory for Tumor Genetics and Regenerative Medicine, Building O48, 4th floor, University Medical Center Eppendorf, Martinistr. 52, 20246 Hamburg, Germany Tel: +49 407 4105 8267; fax: +49 407 4105 9665; e-mail: kluwe@uke.de

Received September 20, 2017

Accepted August 5, 2018

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