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

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.

Sleep Disorders in Menopause: Review of the Literature and Occurrence through Menopausal Stages

We here review principal literature data about sleep disorders in menopause and we compared it with data obtained from a systematical screening of a sample of 161 menopausal women through questionnaires and clinical evaluation. Our data reveal high occurrence of sleep disorders in this group of women if compared to literature data about general population, in the absence of statistically significant differences among the three menopausal stages: we find only a trend toward a higher risk of OSAS (Obstructive Sleep Apnea Syndrome) in PM versus early PM and MT. However, none of women in our survey underwent PSG (polysomnography), essential to confirm the diagnosis of OSAS and none was diagnosed with RLS (Restless Legs Syndrome) (prior to our survey) by the Gynecologist or General Pratictioner: these data reveal the issue of too low attention towards sleep disorders in this contest. Generic “sleep complaints” are clearly associated with depressed mood and worse-quality life along the menopausal process. In our sample, a non-specific definition of insomnia shows a peculiar relationship with a mood disorder: it is only variable not associated with higher BDI and KI scores, in fact. This might suggest that the conditions linked to depression of these women could be more specific sleep disturbances, such as RLS and OSAS.