Expression of vitamin D receptor decreases during progression of pigmented skin lesions
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1,25-dihydroxyvitamin D3 affects proliferation, differentiation, and apoptosis and protects DNA against oxidative damage with a net tumorostatic and anticarcinogenic effect. It acts through a specific nuclear receptor that is widely distributed through the body. Although a beneficial role of vitamin D in melanoma patients has been suggested, there is lack of information on the changes in the expression pattern of vitamin D receptor during progression of pigmented lesions. Using immunohistochemistry, we analyzed the expression of vitamin D receptor in 140 samples obtained form 82 patients, including 25 benign nevi, 70 primary cutaneous melanomas, 35 metastases, 5 re-excisions, and 5 normal skin biopsies. The strongest expression was observed in normal skin that significantly decreased in melanocytic proliferations with the following order of expression: normal skin > melanocytic nevi > melanomas = metastases. The vitamin D receptor expression in skin surrounding nevi and melanoma was also significantly reduced as compared to normal skin. Tumor-infiltrating and lymph node lymphocytes retained high levels of vitamin D receptor. There was negative correlation between tumor progression and vitamin D receptor expression with a remarkable decrease of the immunoreactivity in nuclei of melanoma cells at vertical versus radial growth phases and with metastatic melanomas showing the lowest cytoplasmic receptor staining. Furthermore, lack of the receptor expression in primary melanomas and metastases was related to shorter overall patients' survival. In addition, the receptor expression decreased in melanized melanoma cells in comparison to amelanotic or poorly pigmented cells. Therefore, we propose that reduction or absence of vitamin D receptor is linked to progression of melanocytic lesions, that its lack affects survival of melanoma patients, and that melanogenesis can attenuate receptor expression. In conclusion, changes in vitamin D receptor expression pattern can serve as important variables for diagnosis, predicting clinical outcome of the disease, and/or as a guidance for novel therapy of melanomas based on use of vitamin D or its derivatives.
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VDR and CYP27B1 expression decrease during melanoma progression, and melanization and melanogenesis negatively affect overall and stage III disease survival.
“expression of the VDR and CYP27B1 decreased during melanoma progression, and melanization and melanogenesis negatively affected both overall- and stage III disease-survival”
From The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions (2014) · cites this paper as [81]
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Self-citationVitamin D receptor expression in the mucosal tissue at the gastroesophageal junction
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Calcitriol and Calcidiol Can Sensitize Melanoma Cells to Low–LET Proton Beam Irradiation
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Targeting Melanin in Melanoma with Radionuclide Therapy
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Self-citation
- Authors
- Brożyna, A. A., Jozwicki, W., Janjetovic, Z., & Slominski, A. T.
- Affiliations
- Nicolaus Copernicus University (PL)
- University of Tennessee Health Science Center (US)
- Corresponding author
- Slominski, Andrzej T.
- Venue
- Human Pathology
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 42
- Issue
- 5
- Pages
- 618-631
- ISSN
- 0046-8177 (ISSN-L)
- PMC
- PMC3078192
- OpenAlex
- W2153488515
- Cited by
- 120
- References
- 51
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 9 · 2019: 4 · 2018: 8 · 2017: 10 · 2016: 11 · 2015: 8 · 2014: 12 · 2013: 10 · 2012: 9
- FWCI
- 7.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Pathology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- vitamin D receptor, melanoma, cutaneous melanoma, melanocytic nevi, metastatic melanoma, tumor progression, melanogenesis, patient survival, tumor-infiltrating lymphocytes, radial growth phase, vitamin D supplementation
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cell Nucleus, Elastic Tissue, Female, Humans, Immunohistochemistry, Male, Melanins, Melanoma, Middle Aged, Mitosis, Nevus, Pigmented, Pigmentation Disorders, Skin, Skin Neoplasms, Tumor Cells, Cultured, Ultraviolet Rays, Survival Rate, Apoptosis, Receptors, Calcitriol, Disease Progression, Young Adult
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