Expression of vitamin D3 receptor in kidney tumors

Abstract

The kidney is not only a primary vitamin D target organ but also is a key site of vitamin D metabolism. Recent studies have shown that vitamin D has important physiologic effects on proliferation and differentiation in a variety of benign and malignant cells. Our preliminary immunohistochemical study showed that vitamin D receptor (VDR) was highly expressed in renal distal tubules and collecting ducts, whereas the renal proximal tubules and glomeruli did not express VDR. These observations led us to study the expression of VDR in various kidney tumors to determine the possible diagnostic utility of VDR. Paraffin tissue microarray (TMA) blocks were constructed containing core cylinders from clear cell (52), papillary (35), chromophobe (20), sarcomatoid (20), and metastatic (59) renal cell carcinomas (RCCs). Oncocytomas (20), normal adult kidneys (12), and normal adult adrenals (6) were also included. In addition, 30 clear cell RCCs and 3 collecting duct carcinomas were also studied using conventional sections. Furthermore, VDR messenger RNA and protein expression was also quantified using real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. Vitamin D receptor was strongly positive in collecting duct carcinomas (100% [3/3], cytoplasmic), papillary RCCs (94% [33/35], cytoplasmic), chromophobe RCCs (85% [17/20], membranous), and oncocytomas (90% [18/20], cytoplasmic with perinuclear accentuation). In contrast, VDR expression was focal/weak and present only in the peripheral regions of clear cell RCCs. Vitamin D receptor was weakly positive in sarcomatoid variant RCCs (88% [14/16]) regardless of the type of associated original RCC. Overall, VDR is a discriminative marker for renal cell tumors. The preferential expression of VDR in chromophobe RCCs, oncocytomas, and collecting duct carcinomas is in agreement with the concept that these tumors differentiate toward epithelium lining the distal convoluted tubules and collecting ducts. Considering the different VDR expression patterns, VDR is a useful ancillary tool in distinguishing chromophobe RCCs from oncocytomas. In addition, the focal and much weaker VDR expression in clear cell RCCs makes VDR valuable in distinguishing clear cell RCC from other types of RCCs.