title: Prognostic impact of EMT (epithelial-mesenchymal-transition)-related protein expression in endometrial cancer.
abstract: OBJECTIVE
  The epithelial-mesenchymal-transition (EMT) is an important step in the invasion and metastasis of cancer. A critical molecular feature of this process is the downregulation of E-cadherin expression, which is mainly controlled by Snail-related zinc-finger transcription factors (Snail and Slug). The aim of this study was to evaluate the prognostic impact of EMT-related protein (E-cadherin, Snail and Slug) expression in endometrial cancer.
  
  
  METHODS
  An immunohistochemical analysis was conducted using tissue microarray samples of 354 primary tumors and 30 metastases of endometrial carcinomas, and the relationship between protein expression, clinicopathological features and outcomes were investigated.
  
  
  RESULTS
  Reduced E-cadherin was seen in 39.8% of primary tumors. Reduced E-cadherin was seen in 19.5%, 40.8% and 72.7% of G₁, G₂ and G₃ endometrioid adenocarcinomas, respectively. The nuclear expression of Snail and Slug were positive in 16.9% and 3.7% of primary tumors, respectively. EMT status, which was represented by both reduced E-cadherin and nuclear expression of Snail, was significantly associated with histological type, FIGO stage, myometrial invasion, positive peritoneal cytology and patient survival (p < 0.01). There was no difference in the rates of EMT status between the primary tumors and metastases. A multivariate analysis showed that EMT-positive status was a significant predictor for both the progression-free survival and overall survival (p < 0.01).
  
  
  CONCLUSIONS
  These data indicate that EMT status has a prognostic impact in endometrial cancer. Therefore, the clarification and control of EMT signaling is a promising molecular targeting therapy in endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Terai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Satoe
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Saha
authors.initials: S
authors.lastname: Yoo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsunetoh
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takai
authors.forename: Masanori
authors.initials: M
authors.lastname: Kanemura
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanabe
authors.forename: Masahide
authors.initials: M
authors.lastname: Ohmichi
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002296:Carcinosarcoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D002467:Cell Nucleus / Q000378:metabolism; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors