Immunohistochemical expression of vitamin D receptor in melanocytic naevi and cutaneous melanoma: a case-control study

Puerto, Constanza del; Navarrete‐Dechent, Cristián; Molgó, Montserrat; Camargo, Carlos A.; Borzutzky, Arturo; González, Sergio

doi:10.1111/bjd.16103

Cited by 13 publications

(11 citation statements)

References 23 publications

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“…Del Puerto and co-workers observed higher cytoplasmic VDR levels in nevi than in melanomas, which inversely correlated with Clark level and pTNM staging. However, in their study, nuclear VDR expression was higher in melanomas (232). This surprising pattern might have been secondary to the specificity of the antibodies used in the study (in contrast to our study, the authors used polyclonal antibodies, and did not verify specificity) and use of a different assay method.…”

Section: Serum Vitamin D Level In Patients With Melanomacontrasting

confidence: 80%

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

2019

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Melanoma is one of the most lethal types of skin cancer, with a poor prognosis once the disease enters metastasis. The efficacy of currently available treatment schemes for advanced melanomas is low, expensive, and burdened by significant side-effects. Therefore, there is a need to develop new treatment options. Skin cells are able to activate vitamin D via classical and non-classical pathways. Vitamin D derivatives have anticancer properties which promote differentiation and inhibit proliferation. The role of systemic vitamin D in patients with melanoma is unclear as epidemiological studies are not definitive. In contrast, experimental data have clearly shown that vitamin D and its derivatives have anti-melanoma properties. Furthermore, molecular and clinicopathological studies have demonstrated a correlation between defects in vitamin D signaling and progression of melanoma and disease outcome. Therefore, adequate vitamin D signaling can play a role in the treatment of melanoma. Skin cells are able to activate vitamin D via classical and nonclassical metabolic pathways (1-9). Vitamin D derivatives have anticancer properties and promote differentiation and inhibit proliferation of various cells, including melanoma, the most aggressive and lethal type of skin cancer. In this review, we provide an overview on the endogenous synthesis and activation of vitamin D via classical and non-classical pathways. We also present the association of vitamin D and melanoma based on epidemiological, experimental and clinical evidence, showing that defects in vitamin D signaling correlate with progression of melanoma and disease outcome. Therefore, restoration of the adequate vitamin D signaling can play a role in melanoma therapy. 473 This article is freely accessible online.

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Section: Serum Vitamin D Level In Patients With Melanomacontrasting

confidence: 80%

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

2019

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“…24 Lower levels of VDR and RXRa in exposed areas than in nonexposed areas can explain why our levels of positivity were lower than those in other studies with other levels of sun exposure. 25,26 We had an IN population in primarily exposed areas, which could influence VDR positivity in this group.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor and Retinoid X Receptor Alpha in Melanocytic Benign Lesions and Melanoma

Ocanha‐Xavier

Xavier

Silva

et al. 2023

The American Journal of Dermatopathology

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Vitamin D receptor (VDR) exerts its biological effects when it heterodimerizes to a nuclear receptor of the retinoid family called retinoid X receptor α (RXRα), stimulating or inhibiting DNA transcription. VDR stimulation by vitamin D analogs led to in vitro antiproliferative effects, and experimental RXRα knockout led to loss of proliferation control in melanoma cells. The aim of this study was to determine VDR and RXRα positivity in melanocytic lesions, compared with normal skin species. By immunohistochemistry assays, nuclear VDR, cytoplasmic VDR, and RXRα and RXRα in keratinocytes surrounding melanocytes were evaluated in 77 controls, 92 intradermal nevi, 54 dysplastic nevi, and 83 melanomas in this retrospective cross-sectional study. Nuclear VDR, cytoplasmic VDR, and RXRα were less expressed in exposed areas (P < 0.001, P = 0.0006, and P < 0.001, respectively) than covered areas. All melanocytic lesions had loss of VDR and RXRα comparing with the control group. In the melanoma group, nuclear VDR tended to inversely correlate with the Breslow index (r = −0.11, P = 0.29) but directly correlated with histological regression (P = 0.0293). RXRα inversely correlated with mitosis (r = −0.245; P = 0.0263). We can suggest that sun exposure affected VDR and RXRα immunopositivity. Nuclear VDR tendency of inverse correlation with the Breslow index showed that worse melanomas have a greater loss of VDR. RXRα inversely correlated with mitosis, indicating that RXRα can have a role in proliferation control. VDR and RXRα may participate in the development of melanocytic lesions and be a future target of new studies and directed therapies.

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“…The color reaction was developed using DAB substrate system containing diamino benzidine) Finally, sections were counterstained with mayers haematoxylen solution (clinilab) (R&D Systems). H score (15) was used depending on the percentage of stained cells at x 400 magnification (0: none, 1:<5%, 2:5-25%, 3: 25-75% and 4:>75%), and the intensity of staining (0: absent, 1: weak, 2: moderate, and 3: strong). The immunoreactive score was calculated by multiplying the two parameters with a total score 1-12.…”

Section: Assessment Of Il-36α Expressionmentioning

confidence: 99%

Interleukin-36α Expression in Vitiligo Skin Lesions and Its Association with Disease Pattern, Activity, and Severity

Atef

Mansour

Ibrahim

et al. 2022

Suez Canal University Medical Journal

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Background: Vitiligo is a pigmentary disorder defined by the presence of well-circumscribed milky-white macules on the skin and mucous membranes caused by the loss of functional melanocytes in the affected areas. There are various theories for vitiligo's origin, including neurological, auto cytotoxic, genetic, and immunological theories. Because the cytokine IL-36 is involved in the development and pathophysiology of autoimmune disorders such as psoriasis, rheumatoid arthritis, and SLE, it's probable that IL-36 plays a role in the progression of vitiligo. Objectives: The purpose of this study was to look at the tissue expression of IL-36 in vitiligo lesions and non-lesional skin. Patients and Methods: There were 41 vitiligo patients and 5 healthy controls in this cross-sectional analytic study. Each patient's history was collected, and all patients were examined by a dermatologist to determine the pattern, activity, and severity of vitiligo. Biopsies were extracted from lesional and nonlesional skin of all patients, and immunohistochemistry staining for IL-36 expression was performed. Results: In vitiligo patients, IL-36 expression was elevated in both lesional and nonlesional skin, primarily in the inflammatory infiltrate in the dermis. In terms of age of onset, sex, disease duration, course, activity severity, and pattern, there is no significant variation in IL-36 expression. Conclusion: Our findings suggested that IL 36 may have a role in the etiology of vitiligo, which could shed light on the disease's pathogenesis.

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Immunohistochemical expression of vitamin D receptor in melanocytic naevi and cutaneous melanoma: a case-control study

Abstract: Alterations in VDR expression and localization are found in MM compared with DN. Loss of cytoplasmic VDR was associated with melanoma tumour size, suggesting that loss of cytoplasmic VDR may be a prognostic factor.

Cited by 13 publications

References 23 publications

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Vitamin D Receptor and Retinoid X Receptor Alpha in Melanocytic Benign Lesions and Melanoma

Interleukin-36α Expression in Vitiligo Skin Lesions and Its Association with Disease Pattern, Activity, and Severity

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