title: Coordinate expression of Cdc25B and ER-alpha is frequent in low-grade endometrioid endometrial carcinoma but uncommon in high-grade endometrioid and nonendometrioid carcinomas.
abstract: Overexpression of cdc25B, an important cell cycle regulator, has been shown to result in mammary gland hyperplasia in transgenic mice and to increase steroid hormone responsiveness as a direct coactivator of the estrogen receptor (ER). We investigated the potential role of cdc25B in the pathogenesis of endometrial carcinomas in conjunction with ER-alpha. We examined the expression of cdc25B and phosphorylated ER-alpha in 4 archived human specimens of normal endometrium; 7 endometrial hyperplasia with or without atypia; 32 endometrioid endometrial carcinoma (EEC), including 20 low-grade (grade 1) and 12 high-grade (grade 2 or 3) tumors; and 18 endometrial cancers with aggressive histological subtypes (uterine papillary serous carcinoma and clear cell carcinoma, UPSC/CCC) by immunohistochemistry with monoclonal antibodies. Expression of cdc25B and phosphorylated ER-alpha was increased in endometrial hyperplasia and atypical hyperplasia compared with normal secretory endometrium. Ninety percent (18 of 20) of the low-grade EEC expressed cdc25B at a high level, whereas only 42% (5 of 12) of the high-grade EEC did so (chi(2) = 8.7; P < 0.01). Sixty-five percent (13 of 20) of the low-grade EEC expressed phosphorylated ER-alpha at high levels, but only 17% (2 of 12) of high-grade EEC did so (chi(2) = 7.0; P < 0.01). Coordinate high-level expression of phosphorylated ER-alpha and cdc25B occurred in 65% (13 of 20) of low-grade EEC but in only 17% (2 of 12) of the high-grade EEC (chi(2) = 7.0; P < 0.01). In the UPSC/CCC tumors, only 22% (4 of 18) of the tumors expressed phosphorylated ER-alpha at high-levels. However, 83% (15 of 18) of these carcinomas showed high expression of cdc25B (chi(2) = 13.5; P < 0.01). The majority of the UPSC/CCC (15 of 18) did not show coordinate high expression of phosphorylated ER-alpha and cdc25B. Our findings show that in endometrial hyperplasia and low-grade EEC, coordinate increase in cdc25B and phosphorylated ER-alpha occurs. However, in UPSC/CCC, cdc25B is highly expressed without coordinate increase in phosphorylated ER-alpha. Cdc25B may play important roles in the development and progression of EEC and UPSC/CCC by different mechanisms.
authors.affiliation: Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Wu
authors.forename: Brian M
authors.initials: BM
authors.lastname: Slomovitz
authors.forename: Joseph
authors.initials: J
authors.lastname: Celestino
authors.forename: Linda
authors.initials: L
authors.lastname: Chung
authors.forename: Angela
authors.initials: A
authors.lastname: Thornton
authors.forename: Karen H
authors.initials: KH
authors.lastname: Lu
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000473:pathology; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D018283:Cystadenocarcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000096:biosynthesis; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology; D020687:cdc25 Phosphatases / Q000096:biosynthesis*
chemical_list: D018797:Cell Cycle Proteins; D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C038865:estrogen regulated protein; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases