Expression of dicarbonyl/l‐xylulose reductase (DCXR) in human skin and melanocytic lesions: morphological studies supporting cell adhesion function of DCXR

Abstract

It has been proposed that dicarbonyl/L-xylulose reductase (DCXR) is increased in prostate cancer. Also, when compared with normal skin, a virtual northern blot shows increased expression of DCXR in melanomas. We investigated DCXR expression in a tissue microarray, with 20 benign and 33 malignant melanocytic lesions and possible colocalization of DCXR with cell adhesion molecules using double immunofluorescence/confocal microscopy in normal human skin. Most nevi expressed DCXR in the cytoplasmic membrane, but some melanomas (20-30%) showed loss of membranous expression with inappropriate cytoplasmic or nuclear expression. Perinuclear Golgi expression was found in primary (14%) and metastatic (32%) melanomas showing dishesive growth pattern. Overall, the intensity of expression was stronger in nevi compared with melanomas (p < 0.005). In normal skin, DCXR was colocalized with E-cadherin and beta-catenin at the intercellular membranes of keratinocytes and with CD31 at the intercellular junctions of endothelial cells. DCXR was localized in the cytoplasmic membrane of normal melanocytes. These findings indicate that decreased membranous expression of DCXR with altered subcellular localization appears to be associated with malignant progression of melanocytic lesions. We show for the first time the expression of DCXR in normal keratinocytes, melanocytes and endothelial cells.