title: Immunohistochemical expression of uPA, PAI-1, cathepsin D and apoptotic cells in ductal carcinoma in situ of the breast.
abstract: BACKGROUND
  We examined the relationship between biological markers, apoptotic indices and pathologic subtypes of ductal carcinoma in situ (DCIS) of the breast. The tumor-biological factors can be divided into invasive and proliferative markers. We chose urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and Cathepsin D as invasive markers, and Ki-67 and C-erbB2 oncoproteins as proliferative factors for our study.
  
  
  METHODS
  We used immunohistochemical methods to investigate the expression of uPA, PAI-1, Cathepsin D, Ki-67, C-erbB2 and ssDNA (single-stranded DNA for apoptotic cells) in 20 cases of DCIS. Tumor histological grade and the immunohistochemical expression of invasive and proliferative markers were compared.
  
  
  RESULTS
  Histological grade is associated with C-erbB2, MIB-1, apoptotic index (AI) and expression of PAI-1 in cancer and stroma. The correlation coefficient of the MIB-1 index and AI was 0.867. Of these invasive markers, only expression of PAI-1 in tumor and in stroma was associated with C-erbB2.
  
  
  CONCLUSIONS
  Our results show that the apoptosis index is closely related to the MIB-1 index, and also suggest that the immunohistochemical detection of PAI-1 in the cytoplasm of both carcinoma cells and stromal cells of DCIS is related to histological grade and expression of the proliferative markers MIB-1 and C-erbB2. Therefore, we infer that both invasiveness and proliferation are affected by the tumorigenesis of DCIS.
authors.affiliation: The University of Tokushima, 3-18-5 Kuramoto-cho, Tokushima 770-0052, Japan.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhao
authors.forename: Tadaoki
authors.initials: T
authors.lastname: Morimoto
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sasa
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Izumi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology*; D002402:Cathepsin D / Q000032:analysis / Q000378:metabolism*; D016009:Chi-Square Distribution; D046508:Culture Techniques; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000378:metabolism*; D011336:Probability; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012680:Sensitivity and Specificity; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D002402:Cathepsin D; D019394:Ki-67 Antigen; D017395:Plasminogen Activator Inhibitor 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D014568:Urokinase-Type Plasminogen Activator