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Impact of VDR and RXR expression in non-melanoma skin cancer pathogenesis
Juliana P Ocanha-Xavier1,2, José C C Xavier1,3,4, Márcia Guimarães da Silva1
1Department of Pathology, São Paulo State University, UNESP, São Paulo, Brazil.
Abstract:
1,25(OH)2 D3 , the active form of vitamin D, has been extensively studied for its putative protective activities against tumors. It does biological work by connecting to a nuclear receptor called VDR, which heterodimerizes itself to another nuclear receptor, RXR. The study observed differences in VDR and RXR expression in non-melanoma skin cancer a actinic keratosis and compared it with normal skin. We performed VDR and RXR immunohistochemistry of 76 controls (normal skin), 49 actinic keratosis, 99 basal cell carcinomas and 96 squamous cell carcinomas from formalin-fixed paraffin-embedded, resulting from surgical procedures. There was a clear pattern in the control group (p < 0.001), with the positivity of both receptors, VDR and RXR. Actinic keratosis differed from the basal cell carcinoma and control groups concerning RXR expression (p < 0.001). SCC was negative for both receptors, differing in all groups (p < 0.001). The site of positivity (nuclear, cytoplasmatic or both) of VDR differed between all groups (p < 0.001). To date, our series is the largest of VDR and RXR immunohistochemistry concerning non-melanoma skin cancer. Our findings reinforce the need to understand the pathways involving VDR and RXR to direct therapies and prevention manoeuvres.
Insights
The active vitamin D (1,25(OH)2D3) pathway, involving vitamin D receptor (VDR) and retinoid X receptor (RXR), shows altered expression in non-melanoma skin cancers. Squamous cell carcinoma notably lacks both VDR and RXR.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- The active form of vitamin D, 1,25(OH)2D3, is investigated for anti-tumor properties.
- Vitamin D exerts its effects through the vitamin D receptor (VDR), which forms a complex with the retinoid X receptor (RXR).
- Altered VDR and RXR expression is implicated in various cancers, including non-melanoma skin cancer (NMSC).
Purpose of the Study:
- To investigate and compare the expression patterns of VDR and RXR in normal skin, actinic keratosis (AK), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC).
- To determine if VDR and RXR expression levels and localization correlate with different NMSC subtypes.
Main Methods:
- Immunohistochemistry was performed on tissue samples from 76 normal skin controls, 49 AKs, 99 BCCs, and 96 SCCs.
- VDR and RXR expression (positivity and localization) was analyzed across the different skin conditions.
Main Results:
- A clear pattern of VDR and RXR positivity was observed in the normal skin control group.
- Actinic keratosis showed distinct RXR expression compared to BCC and control groups.
- Squamous cell carcinoma samples were negative for both VDR and RXR, significantly differing from all other groups.
- The localization of VDR positivity (nuclear, cytoplasmic, or both) varied significantly across all groups.
Conclusions:
- This study presents the largest series to date examining VDR and RXR immunohistochemistry in NMSC.
- Findings highlight significant alterations in VDR and RXR expression and localization in NMSC development.
- Understanding these VDR-RXR pathway alterations is crucial for developing targeted therapies and prevention strategies for NMSC.
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