Journal Article

Immunohistochemical evaluation of vitamin D receptor（VDR） expression in cutaneous melanoma tissues and four VDR gene polymorphisms

Francesco La Marra Giuseppe Stinco Cinzia Buligan Giovanni Chiriacò Diego Serraino Carla Di Loreto Sabina Cauci

2017

Overview

Objective：Vitamin D receptor（VDR）mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene（VDR）polymorphisms.Methods：We evaluated VDR protein expression（by monoclonal antibody immunostaining）,melanoma characteristics,and carriage of VDR-Fok I-rs2228570（C〉T）,VDR-Bsm I-rs1544410（G〉A）,VDR-ApaI-rs7975232（T〉G）,and VDR-TaqI-rs731236（T〉C）polymorphisms（by restriction fragment length polymorphism）.Absence or presence of restriction site was denoted by a capital or lower letter,respectively：＂F＂and＂f＂for Fok I,＂B＂and＂b＂for Bsm I,＂A＂and＂a＂for ApaI,and ＂T＂and＂t＂for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas（52.1±12.7 years old）were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows：100% positive vs.〈100%;over the median 20%（high VDR expression）vs.≤20%（low VDR expression）;absence vs.presence of VDR-expressing cells.Results：Stage I melanomas,Breslow thickness of〈1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.〈100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression（odds ratio=14.5;P=0.025）.VDR expression was not associated with metastasis,ulceration,mitosis〉1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions：We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.

• Subject: VDR / 免疫组织 / 化学研究 / 基因多态性 / 皮肤癌 / 维生素D受体 / 限制性片段长度多态性 / 黑色素瘤