Receptors, Calcitriol; VDR protein, human; Humans; Alleles; Receptors, Calcitriol/genetics; Skin; Melanoma/genetics; Skin Neoplasms/genetics; cutaneous melanoma; vitamin D receptor; vitamin D receptor polymorphisms; Melanoma; Skin Neoplasms; Oncology; Dermatology; Cancer Research
Abstract :
[en] Decrease of vitamin D receptor (VDR) expression is observed in melanocytic naevi and melanoma compared to normal skin. Little is known about factors influencing VDR expression in cutaneous melanoma (CM). We investigated the correlation of VDR expression in CM with 25-hydroxy vitamin D (25OHD) levels, demographic/clinical parameters, genetic variants of VDR and pathology of the primary tumor. Demographic/clinical parameters were recorded in 407 prospectively recruited CM patients of a multi-center controlled study (ViDMe trial). We determined VDR expression both in the nucleus and in the cytoplasm by semi-quantitative assessment in CM tissue using histochemistry in 279 patients, expressed in percentages and histoscore (H-score). Genomic DNA from 332 patients was extracted to genotype thirteen VDR single nucleotide polymorphisms (SNPs) using TaqMan. VDR expression in CM tissue from 279 patients was correlated with clinical/demographic parameters and 25OHD levels (univariable and multivariable analysis), VDR SNPs (univariable analysis) and pathology parameters of primary CM tissue (univariable analysis). Cytoplasmic VDR expression was increased in patients who stated to have a high sun exposure during their life compared to patients with low sun exposure (p H-score,univariable : 0.001, p H-score,multivariable : 0.004). The A allele of the genetic VDR polymorphism Fok1 was associated with a higher expression of the VDR in the cytoplasm (p cytoplasmic, univariable : 0.001 and p H-score, univariable : 0.02). In the primary tumor, presence of mitosis (p nucleus,%, univariable : 0.002) and perineural invasion (p nucleus,%,univariable : 0.03) were significantly associated with low nuclear VDR expression. ClinicalTrials.gov Identifier: NCT01748448.
Disciplines :
Dermatology
Author, co-author :
De Smedt, Julie; Laboratory of Dermatology, Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
Aura, Claudia; Conway Institute of Biomolecular and Biomedical Research, Pathology, University College Dublin, Dublin
Van Kelst, Sofie; Laboratory of Dermatology, Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
Janssen, Laudine; Laboratory of Dermatology, Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
Marasigan, Vivien; Department of Surgery, South Infirmary Victoria University Hospital, Cork, Ireland
Boecxstaens, Veerle; Oncological and Vascular Access Surgery, Department of Surgical Oncology
Stas, Marguerite; Oncological and Vascular Access Surgery, Department of Surgical Oncology
Bogaerts, Kris; Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat
Belmans, Ann; Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat
Cleynen, Isabelle; Laboratory for Complex Genetics, Department of Human Genetics, KU Leuven
Vanderschueren, Dirk; Clinical and Experimental Endocrinology, Department of Chronical Illness and Metabolism, KU Leuven, UZ Leuven
Vandenberghe, Katleen; Department of Cardiovascular Sciences, KU Leuven
Bechter, Oliver; Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, UZ Leuven, Leuven
Nikkels, Arjen ; Université de Liège - ULiège > Département des sciences cliniques > Dermatologie
Strobbe, Tinne; Department of Dermatology, Imeldaziekenhuis, Bonheiden, Belgium
Emri, Gabriella; Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Lambrechts, Dieter; Laboratory for Translational Genetics, Department of Oncology, KU Leuven ; Center for Cancer Biology (VIB), Leuven, Belgium
Garmyn, Marjan; Laboratory of Dermatology, Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
European Cancer Information System. https://ecis.jrc.ec.europa.eu/explorer.php?$0-0$1-All$4-1,2$3-27$6-0,85$5-2020, 2020$7-7$2-All$CEstByCountry$X0_8-3$X0_19-AE27$X0_ 20-No$CEstBySexByCountry$X1_8-3$X1_19-AE27$X1_-1-1 $CEstByIndiByCountry$X2_8-3$X2_19-AE27$X2_20-No$CEstRelative $X3_8-3$X3_9-AE27$X3_19-AE27$CEstByCountryTable$X4_19-AE27
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