title: Nrf2 expression in endometrial serous carcinomas and its precancers.
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 patho-genesis. 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) and verified by using Western blots. 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.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yi
authors.forename: Nisreen
authors.initials: N
authors.lastname: Abushahin
authors.forename: Shujie
authors.initials: S
authors.lastname: Pang
authors.forename: Donna
authors.initials: D
authors.lastname: Zhang
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
authors.forename: Wenxin
authors.initials: W
authors.lastname: Zheng
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human