title: High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression.
abstract: BACKGROUND
  Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression.
  
  
  METHODS
  Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer.
  
  
  RESULTS
  The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies.
  
  
  CONCLUSIONS
  The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer.
authors.affiliation: Cell and Antibody Analysis, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Maaloev, Denmark. fle@life.ku.dk
authors.forename: Frederikke Lihme
authors.initials: FL
authors.lastname: Egerod
authors.forename: Annette
authors.initials: A
authors.lastname: Bartels
authors.forename: Niels
authors.initials: N
authors.lastname: Fristrup
authors.forename: Michael
authors.initials: M
authors.lastname: Borre
authors.forename: Torben F
authors.initials: TF
authors.lastname: Ørntoft
authors.forename: Martin B
authors.initials: MB
authors.lastname: Oleksiewicz
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.forename: Lars
authors.initials: L
authors.lastname: Dyrskjøt
mesh_terms: D018450:Disease Progression; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D051766:Early Growth Response Protein 1