title: Relation between outcomes and expression of estrogen receptor-α phosphorylated at Ser(167) in endometrioid endometrial cancer.
abstract: Both ligand-dependent and ligand-independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation and results in activation of the ERα-dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is also known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and MAPK/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated-ERα at Ser(167) (p-Ser(167) -ERα). However, the expression of p-Ser(167) -ERα in EEC and its prognostic role in ECC is largely unexplored. The purpose of the present study was to investigate the expression of p-Ser(167) -ERα in ECC and its relationship with prognosis. Immunohistochemical staining of primary EEC surgical specimens (n = 103) was carried out using antibodies specific for p-Ser(167) -ERα and for p-mTOR/p-S6K1 and p-MAPK/p-RSK. The correlation of p-Ser(167) -ERα expression with clinicopathological features and survival of ECC was studied. Patients that were positive for nuclear p-Ser(167) -ERα had significantly shorter relapse-free survival, and although the result was not significant, levels of nuclear p-Ser(167) -ERα tended to be higher in advanced-stage ECC patients. Nuclear p-Ser(167) -ERα was significantly positively correlated with p-MAPK and p-S6K1, and with significantly shorter relapse-free survival in EEC.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kato
authors.forename: Makoto
authors.initials: M
authors.lastname: Orisaka
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Chino
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Akiko
authors.initials: A
authors.lastname: Shinagawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yoshida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000401:mortality; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D051057:Proto-Oncogene Proteins c-akt
keywords: Endometrial cancer; location; outcome; p-S6K1; p-Ser167-ERα