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Int J Clin Exp Pathol 2013;6(11):2419-2429
Original Article
Expression of aldo-keto reductase family 1 member C3 (AKR1C3) in neuroendocrine
tumors & adenocarcinomas of pancreas, gastrointestinal tract, and lung
Theodore S Chang, Hsueh-Kung Lin, Kyle A Rogers, Lacy S Brame, Matthew M Yeh, Qing Yang, Kar-Ming Fung
Departments of Pathology, Urology, College of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center,
Oklahoma City, OK; Department of Pathology, University of Washington School of Medicine, Seattle, WA; Department of Pathology, Veterans
Administration Medical Center, Oklahoma City, OK
Received September 22, 2013; Accepted October 15, 2013; Epub October 15, 2013; Published November 1, 2013
Abstract: Human aldo-keto reductase family 1 member C3 (AKR1C3) was initially identified as an enzyme in reducing 5α-dihydrotestosterone
(5α-DHT) to 5α-androstane-3α, 17β-diol (3α-diol) and oxidizing 3α-diol to androsterone. It was subsequently demonstrated to possess
ketosteroid reductase activity in metabolizing other steroids including estrogen and progesterone, 11-ketoprostaglandin reductase activity in
metabolizing prostaglandins, and dihydrodiol dehydrogenase x (DDx) activity in metabolizing xenobiotics. AKR1C3 was demonstrated in sex
hormone-dependent tissues including testis, breast, endometrium, and prostate; in sex hormone-independent tissues including kidney and
urothelium. Our previous study described the expression of AKR1C3 in squamous cell carcinoma and adenocarcinoma but not in small cell
carcinoma. In this report, we studied the expression of AKR1C3 in normal tissue, adenocarcinomas (43 cases) and neuroendocrine (NE)
tumors (40 cases) arising from the aerodigestive tract and pancreas. We demonstrated wide expression of AKR1C3 in superficially located
mucosal cells, but not in NE cells. AKR1C3-positive immunoreactivity was detected in 38 cases (88.4%) of adenocarcinoma, but only in 7
cases (17.5%) of NE tumors in all cases. All NE tumors arising from the pancreas and appendix and most tumors from the colon and lung
were negative. The highest ratio of positive AKR1C3 in NE tumors was found in tumors arising from the small intestine (50%). These results
raise the question of AKR1C3’s role in the biology of normal mucosal epithelia and tumors. In addition, AKR1C3 may be a useful adjunct
marker for the exclusion of the NE phenotype in diagnostic pathology. (IJCEP1309055).
Keywords: Aldo-keto reductase family 1 member C3 (AKR1C3), neuroendocrine tumors, adenocarcinomas, pancreas, gastrointestinal tract,
lung, immunohistochemistry
Address correspondence to: Dr. Kar-Ming Fung, BMSB 451, 940 Stanton Young Blvd., Oklahoma City, OK 73104. Tel: 405-271-5653; Fax: 405-
271-2524; E-mail: karming-fung@ouhsc.edu
Original Article
Expression of aldo-keto reductase family 1 member C3 (AKR1C3) in neuroendocrine
tumors & adenocarcinomas of pancreas, gastrointestinal tract, and lung
Theodore S Chang, Hsueh-Kung Lin, Kyle A Rogers, Lacy S Brame, Matthew M Yeh, Qing Yang, Kar-Ming Fung
Departments of Pathology, Urology, College of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center,
Oklahoma City, OK; Department of Pathology, University of Washington School of Medicine, Seattle, WA; Department of Pathology, Veterans
Administration Medical Center, Oklahoma City, OK
Received September 22, 2013; Accepted October 15, 2013; Epub October 15, 2013; Published November 1, 2013
Abstract: Human aldo-keto reductase family 1 member C3 (AKR1C3) was initially identified as an enzyme in reducing 5α-dihydrotestosterone
(5α-DHT) to 5α-androstane-3α, 17β-diol (3α-diol) and oxidizing 3α-diol to androsterone. It was subsequently demonstrated to possess
ketosteroid reductase activity in metabolizing other steroids including estrogen and progesterone, 11-ketoprostaglandin reductase activity in
metabolizing prostaglandins, and dihydrodiol dehydrogenase x (DDx) activity in metabolizing xenobiotics. AKR1C3 was demonstrated in sex
hormone-dependent tissues including testis, breast, endometrium, and prostate; in sex hormone-independent tissues including kidney and
urothelium. Our previous study described the expression of AKR1C3 in squamous cell carcinoma and adenocarcinoma but not in small cell
carcinoma. In this report, we studied the expression of AKR1C3 in normal tissue, adenocarcinomas (43 cases) and neuroendocrine (NE)
tumors (40 cases) arising from the aerodigestive tract and pancreas. We demonstrated wide expression of AKR1C3 in superficially located
mucosal cells, but not in NE cells. AKR1C3-positive immunoreactivity was detected in 38 cases (88.4%) of adenocarcinoma, but only in 7
cases (17.5%) of NE tumors in all cases. All NE tumors arising from the pancreas and appendix and most tumors from the colon and lung
were negative. The highest ratio of positive AKR1C3 in NE tumors was found in tumors arising from the small intestine (50%). These results
raise the question of AKR1C3’s role in the biology of normal mucosal epithelia and tumors. In addition, AKR1C3 may be a useful adjunct
marker for the exclusion of the NE phenotype in diagnostic pathology. (IJCEP1309055).
Keywords: Aldo-keto reductase family 1 member C3 (AKR1C3), neuroendocrine tumors, adenocarcinomas, pancreas, gastrointestinal tract,
lung, immunohistochemistry
Address correspondence to: Dr. Kar-Ming Fung, BMSB 451, 940 Stanton Young Blvd., Oklahoma City, OK 73104. Tel: 405-271-5653; Fax: 405-
271-2524; E-mail: karming-fung@ouhsc.edu
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