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

Abstract

<h3>Objective:</h3> Vitamin D receptor (VDR) mediates vitamin D activity. We examined whether VDR expression in excised melanoma tissues is associated with VDR gene (<i>VDR</i>) polymorphisms. <h3>Methods:</h3> We evaluated VDR protein expression (by monoclonal antibody immunostaining), melanoma characteristics, and carriage of <i>VDR</i>-FokI-rs2228570 (C&gt;T),<i>VDR</i>-BsmI-rs1544410 (G&gt;A),<i>VDR</i>-ApaI-rs7975232 (T&gt;G), and<i>VDR</i>-TaqI-rs731236 (T&gt;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 FokI, " B” and " b” for BsmI, " 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<i>vs</i>. &lt;100%; over the median 20% (high VDR expression) <i>vs</i>. ≤20% (low VDR expression); absence <i>vs</i>. presence of VDR-expressing cells. <h3>Results:</h3> Stage I melanomas, Breslow thickness of &lt;1.00 mm, level II Clark invasion, Aa heterozygous genotype, and AaTT combined genotype were more frequent in melanomas with high <i>vs</i>. low VDR expression. Combined genotypes BbAA, bbAa, AATt, BbAATt, and bbAaTT were more frequent in 100% <i>vs</i>. &lt;100% VDR-expressing cells. Combined genotype AATT was more frequent in melanomas lacking VDR expression (odds ratio=14.5; <i>P</i>=0.025). VDR expression was not associated with metastasis, ulceration, mitosis &gt;1, regression, tumor-infiltrating lymphocytes, tumoral infiltration of vascular tissues, additional skin and non-skin cancers, and melanoma familiarity. <h3>Conclusions:</h3> We highlighted that <i>VDR</i> 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 <i>VDR</i> genotype may become precise medicinal tools for melanoma in the future.