title: Plasminogen activator system localization in 60 cases of ductal carcinoma in situ.
abstract: BACKGROUND
  The lack of prognostic factors in ductal carcinoma in situ (DCIS) that reliably identifies biologically aggressive tumors adversely affects optimal management. The urokinase-type plasminogen activator (uPA) system, comprised of its receptor, uPAR, and its inhibitor (PAI-1), are critical elements for tumor invasion and their expression in invasive breast cancer can predict clinical outcome. Expression of the uPA system in DCIS may be relevant in defining histological subsets of DCIS with invasive potential.
  
  
  METHODS
  Localization of uPA, uPAR, and PAI-1 was investigated immunohistochemically in 60 DCIS tumors. FISH experiments were performed to determine whether uPA was present in cancer cells themselves or derived from stromal elements.
  
  
  RESULTS
  uPA was ubiquitously expressed in the malignant ductal epithelium of 95% (57/60) of DCIS tumors studied. uPA-mRNA was detected in the malignant ductal epithelium but not the adjacent normal ductal epithelium and stromal elements. uPAR was expressed in 27% (6/22) of high-grade and 24% (9/38) of non-high-grade DCIS. In comparing coexpression, uPA and uPAR were coexpressed in only 25% (15/60) of tumors. PAI-1 was infrequently expressed in high grade (3/22) and absent in non-high-grade DCIS.
  
  
  CONCLUSIONS
  This study identifies the presence of uPA, uPAR, and PAI-1 in both high-grade and non-high-grade DCIS. It may be speculated that coexpression of uPA and its receptor may identify subsets of DCIS with an increased risk for progression to invasive disease. If so, then expression of uPA system components may have prognostic and therapeutic significance in DCIS.
authors: Department of Surgery, University of Texas Health Sciences at San Antonio, USA.
authors: Thelma C
authors: TC
authors: Hurd
authors: Sheila
authors: S
authors: Sait
authors: Shin
authors: S
authors: Kohga
authors: Janet
authors: J
authors: Winston
authors: Maisie
authors: M
authors: Martinick
authors: Rakhee
authors: R
authors: Saxena
authors: Heather
authors: H
authors: Lankes
authors: Gabor
authors: G
authors: Markus
authors: Shashi
authors: S
authors: Harvey
authors: John F
authors: JF
authors: Gibbs
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator