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Int J Clin Exp Pathol 2011;4(1):85-96

Original Article
Nrf2 expression in endometrial serous carcinomas and its precancers

Ning Chen, Xiaofang Yi, Nisreen Abushahin, Shujie Pang, Donna Zhang, Beihua Kong, Wenxin Zheng

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, China
Department of Pathology, University of Arizona College of Medicine, Tucson, AZ
Hospital of Obstetrics and Gynecology, Shanghai Medical College Fudan University, China
Department of Pathology, Tianjin Central Hospital of Obstetrics and Gynecology, China
Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ
Department of Obstetrics and Gynecology, University of Arizona, Tucson, AZ
Arizona Cancer Center, University of Arizona, Tucson, AZ

Received December 17, 2010; accepted December 23, 2010; Epub December 24, 2010; published January 1, 2011

Abstract: Endometrial serous carcinoma (ESC) is the most aggressive subtype of endometrial cancer. Its aggressive behavior and poor
clinical outcome may be partially attributed to lack of early diagnostic markers and unclear pathogenesis. The transcription factor Erythroid--E2-
related factor 2 (Nrf2) is a recently identified protein marker, which plays a role in carcinogenesis as well as responsible for poor prognosis of
many human cancers. The aim of this study is to determine the Nrf2 expression in benign endometrium (n=28), endometrial cancers (n=122)
as well as their precursor lesions (n=81) trying to see whether Nrf2 has any diagnostic usage and is potentially involved in endometrial
carcinogenesis. The level of Nrf2 was evaluated by immunohistochemical (IHC) staining in endometrial samples and representative tissue
samples were verified for Nrf2 expression by using Western blots. The extent and intensity of Nrf2 expression was semi-quantitatively
determined and scored for all samples. An ESC with known Nrf2 overexpression was used as positive control for each IHC run. Among the
malignant cases, Nrf2 was positive in 28 (68%) of 50 ESCs, which was significantly more than in 3 (6%) of 50 endometrioid carcinomas (p <
0.001) and 2 (13%) of 15 clear cell carcinomas (p = 0.001) and other histologic types of endometrial cancers. Among endometrial precursor
lesions, both serous endometrial glandular dysplasia (EmGD, 40%) and serous endometrial intraepithelial carcinoma (EIC, 44%) showed a
significantly higher Nrf2 expression than that in atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (0%), clear cell EmGD
(10%), and clear cell EIC (25%), respectively. We conclude that Nrf2 overexpression is closely associated with endometrial neoplasms with
serous differentiation. Alteration of Nrf2 expression may represent one of the early molecular events in ESC carcinogenesis and
overexpression of Nrf2 may used as a diagnostic marker in surgical pathology. (IJCEP1012009).

Keywords: Nrf2, endometrial cancer, endometrial serous carcinoma, endometrial glandular dysplasia, endometrial intraepithelial carcinoma

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Address all correspondence to:
Wenxin Zheng, MD
Department of Pathology
University of Arizona
1501 N. Campbell Avenue, #5224A
Tucson, AZ 85724, USA.

Beihua Kong, M.D., Ph.D
Qilu Hospital, Shandong University
107 W. Wenhua Road
Ji’nan, Shandong, China 250012