title: Loss of the cell polarity determinant human Discs-large is a novel molecular marker of nodal involvement and poor prognosis in endometrial cancer.
abstract: Recent Drosophila studies showed that Discs-large (Dlg) is critical for regulation of cell polarity and tissue architecture. We investigated the possibility that loss of the human homologue of Drosophila Dlg (DLG1) is involved in endometrial carcinogenesis.
  
  
  
  We analysed DLG1 expression in 160 endometrial cancers by immunohistochemical staining. Its expression was confirmed by quantitative real-time PCR (RT-PCR). We investigated the roles of DLG1 in growth and invasion by knockdown experiment in endometrial cancer cell lines.
  
  
  
  Human DLG1 localises at cellular membrane in normal endometrial tissues. Loss of DLG1 was observed in 37 cases (23.1%). Loss of DLG1 was observed in patients with advanced stage and high-grade histology. It was also observed in patients with nodal metastasis, deep myometrial invasion, and negative oestrogen and progesterone receptors. Patients with loss of DLG1 showed poorer overall survival (P=0.0019). Immunohistochemistry data correlated with RT-PCR data. Knockdown of Dlg1 in endometrial cancer cells resulted in accelerated tumour migration and invasion in vitro.
  
  
  
  Tissue polarity disturbance because of loss of DLG1 was shown to confer more aggressive characteristics to endometrial cancer cells. Our study revealed that DLG1 expression is a novel molecular biomarker of nodal metastasis, high-grade histology, and poor prognosis in endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Sugihara
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Pathology, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sasajima
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ichinose
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Hiraike
authors.affiliation: Department of Pathology, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Fukuo
authors.initials: F
authors.lastname: Kondo
authors.affiliation: Department of Pathology, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.affiliation: Department of Pathology, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ayabe
mesh_terms: D016764:Cell Polarity; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D014162:Transfection