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Int J Clin Exp Pathol 2010;3(2):147-155

Original Article
Expression of AKR1C3 in renal cell carcinoma, papillary urothelial carcinoma, and Wilms’
tumor

Joseph T. Azzarello, Hsueh-Kung Lin, Awet Gherezghiher, Vladislav Zakharov, Zhongxin Yu, Bradley P. Kropp, Daniel J. Culkin, Trevor M.
Penning, and Kar-Ming Fung

Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; Department of Physiology, University of
Oklahoma Health Sciences Center, Oklahoma City, OK 73104; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK 73104;
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; Center of Excellence in Environmental
Toxicology, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Received September 28, 2009; Accepted October 23, 2009; Available online November 15, 2009

Abstract: Human aldo-keto reductase (AKR) 1C3 is a monomeric cytoplasmic multifunctional enzyme that reduces ketosteroids,
ketoprostaglandins, and lipid aldehydes.  AKR1C3 was initially identified as an enzyme involved in steroid metabolism.  However,
immunohistochemistry has demonstrated AKR1C3 in normal adult kidneys with expression in Bowman’ capsule, the mesangial cells,
proximal and distal tubules, as well as mature urothelial epithelium.  The significance of its spatial distribution and metabolic activities in the
kidney remains undefined.  In addition to its ability to catalyze steroid hormones (including androgen, cortisol, and progesterone) and
involvement in prostaglandins metabolism, we suspect that AKR1C3 may function as a chemical barrier in the renal tubules for normal
functioning in mature kidney.  Moreover, AKR1C3 may represent a developmental marker for some urological epithelial tissues.  In this study,
we demonstrate widespread expression of AKR1C3 in renal neoplasms with phenotype recapitulating mature kidney (i.e., renal cell
carcinoma) and urothelium also known as transitional epithelium (i.e., papillary urothelial carcinoma), but limited AKR1C3 expression in renal
neoplasms with phenotype recapitulating embryonic kidneys (i.e., Wilms’ tumor).  Our results suggest that AKR1C3 may represent a
developmental marker that is related to renal epithelium maturity. (IJCEP909003).

Key words: Aldo-keto reductase, renal cell carcinoma, papillary urothelial carcinoma, Wilms’ tumor, kidney cancer

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Address all correspondence to:
Kar-Ming Fung, MD, PhD
Department of Pathology
University of Oklahoma Health Sciences Center
Oklahoma City, OK 73104
E-mail: karming-fung@ouhsc.edu