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Vitamin D and Retinoid X receptors presence in premalignant and malignant skin lesions: comparative study


Introduction: 25-OH-Vitamin D, activated form of vitamin D is in the center of scientific discussion because of its antioxidative properties, and also by its effects in proliferation, cell differentiation and apoptosis. Some studies showed association between of serum level of vitamin D and decrease of cancer risk. This question is quite intriguing about skin because most part of vitamin D is acquired by sun exposure, which is pointed as cause of almost all skin cancers.Vitamin D receptors (VDR) dimerize with retinoid nuclear receptors and influence cell cycle, making mitosis speed become slow. There are several types of retinoid receptors, such as RXR, RAR and their subunits that gather as a superfamily of nuclear receptors. VDR links mainly to RXR receptors. Most studies tell loss of RXR in tumor cells. Retinoids (derived from vitamin A) action in skin cancers can be demonstrated in chemoprevention of patients with high carcinogenic potential syndromes, such as Xeroderma pigmentosum and Gorlin's syndrome. Material and Methods: Paraffined histopathological samples from Clinics' Hospital of Botucatu School Medicine, from the period of 2012 to 2017, will be submitted to immunohistochemistry study to verify VDR and RXR presence. This study was submitted and approved by Institutional Review Board (registration number : 03058918.4.0000.5411).100 controls, 90 actinic keratosis, 100 basal cell carcinomas, 100 spindle cell carcinomas, 100 intradermal nevi, 100 dysplastic nevi and 100 melanomas were included.Control cases were obtained in margins enhancement sample in the absence of residual tumor. Non-nodular basal cell carcinomas and non-intradermal nevi were also excluded as well as coalition lesions. Deteriorated samples, without condition to realize immunohistochemistry and lesions of unknown localization shall be excluded.Samples will be separated according to their site (exposed or not exposed) in order to verify if receptors presence suffers influence from sun exposure. Paraffin blocks will be submitted to immunohistochemistry to VDR (Santa Cruz or Abcam) and to RXR receptors (Novus or Abcam) following manufacturer instructions. They will be evaluated in a multiheaded microscope by two dermatopathologists and one dermatologist that in agreement will define grade of positivity of the receptors.At the same time, we will analyze in paraffined material, by platform NanoString nCounter 24 controls, 24 intradermic nevi, 24 dysplastic nevi, 24 actinic keratosis, 24 basal cell carcinomas, 24 spindle cell carcinomas and 48 melanomas. In this platform we will verify genic expression of these two receptors (VDR and RXR) and also 22 genes related to their signaling pathway. It consists of a technology that allows counting and detection of genes through a barcode fluorescent digital system. Thus, we will have a intern control of immuno-histochemistry results and we will be allowed to study genic pathway common to both receptors. (AU)

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