Original Article Suppressed expression of type 2 3α/type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) in endometrial hyperplasia and carcinoma
Vladislav Zakharov, Hsueh-Kung Lin, Joseph Azzarello, Scott McMeekin, Kathleen N. Moore, Trevor M. Penning, and Kar-Ming Fung
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma City Department Veterans Affairs Medical Center, Oklahoma City, OK, USA; Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Received June 28, 2010, accepted June, 2010, available online July, 2010
Abstract: The diagnosis of endometrial hyperplasia and endometrial type adenocarcinoma arising within the uterine cavity has long been rested on morphologic criteria. Although distinction between normal endometrial epithelium from adenocarcinoma is usually straightforward, the separation between normal and hyperplastic endometrium, particularly those cases without atypia, can be a diagnostic challenge. The same is true in separation of hyperplastic endometrium with atypia from endometrial-type endometrial adenocarcinoma. Type 2 3α-/type 5 17β- hydroxysteroid dehydrogenase (HSD) (AKR1C3) is a multifunctional enzyme involved in androgen, estrogen, progesterone, and prostaglandin metabolism. Its expression has been shown in the epithelium of the renal tubules, urothelial epithelium, and endothelial cells in normal tissues as well as in prostatic adenocarcinoma. The proliferation and maintenance of endometrial epithelium is dependent on both estrogen and progesterone; and AKR1C3-mediated steroid metabolism may play a critical role in the maintenance of viable normal and abnormal endometrial epithelium. We studied the expression of AKR1C3 in 33 endometrial biopsy specimens including 13 cases of normal proliferative endometrium, 8 cases of hyperplastic endometrium with and without atypia, and 12 cases of primary endometrial adenocarcinoma of endometrial type. We demonstrated a uniform, diffuse, and strong expression of AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. In contrast, the expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium. These findings suggest that AKR1C3 may play important roles in the physiology of endometrial cells and that suppressed AKR1C3 expression may represent a feature that allows differentiation of hyperplastic and neoplastic endometrial epithelium from normal endometrial epithelium. However, reduced AKR1C3 expression cannot distinguish hyperplastic endometrium from endometrial adenocarcinoma of endometrial type. The biologic and pathological roles of AKR1C3 in endometrial epithelium require further investigation.(IJCEP1006008).
Address all correspondence to: Kar-Ming Fung, M.D., Ph.D. Department of Pathology University of Oklahoma Health Sciences Center Rm. 451, 940 Stanton Young Blvd. Oklahoma City, OK 73104 Tel: (405) 271-5653 E-mail: firstname.lastname@example.org