Impact of VDR and RXR expression in non-melanoma skin cancer pathogenesis

Exp Dermatol. 2022 Aug;31(8):1202-1207. doi: 10.1111/exd.14574. Epub 2022 Apr 10.

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.

Keywords: actinic; basal cell; calcitriol; carcinoma; keratosis; receptors; retinoid X receptor alpha; squamous cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Basal Cell*
  • Carrier Proteins
  • Humans
  • Keratosis, Actinic*
  • Receptors, Calcitriol / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Retinoid X Receptors / metabolism
  • Skin Neoplasms*

Substances

  • Carrier Proteins
  • Receptors, Calcitriol
  • Receptors, Cytoplasmic and Nuclear
  • Retinoid X Receptors
  • VDR protein, human