title: Urokinase plasminogen activator, a strong independent prognostic factor in breast cancer, analysed in steroid receptor cytosols with a luminometric immunoassay.
abstract: Urokinase plasminogen activator (uPA) is involved in the activation of different proteases which participate in the degradation of extracellular matrix, thereby enhancing the invasive capacity of tumour cells. uPA has been shown to be of prognostic importance in breast cancer. We have analysed uPA with a new luminometric immunoassay (LIA), applicable in cytosol samples routinely used for oestrogen-receptor (ER) and progesterone-receptor (PgR) analyses. At a cut-off value of 0.62 ng uPA/mg protein, 33% (230/688) samples were classified as representing high uPA tumours. High uPA content was found to be associated with shorter recurrence-free survival (median observation time: 42 months), ER and PgR negativity, increased p53 expression, DNA non-diploidy and a high S-phase fraction (SPF), but not with lymph node involvement or tumour size (< or = 20 mm versus > 20 mm). In the subgroup of patients not treated with systemic adjuvant therapy, multivariate analysis showed uPA to be an independent prognostic factor together with lymph node status and SPF. If these results can be reproduced, uPA may be a factor suitable for inclusion in a prognostic index.
authors.affiliation: Department of Oncology, University Hospital, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Fernö
authors.forename: P O
authors.initials: PO
authors.lastname: Bendahl
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: J
authors.initials: J
authors.lastname: Brundell
authors.forename: L
authors.initials: L
authors.lastname: Hirschberg
authors.forename: H
authors.initials: H
authors.lastname: Olsson
authors.forename: D
authors.initials: D
authors.lastname: Killander
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D017024:Chemotherapy, Adjuvant; D003600:Cytosol / Q000201:enzymology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D013629:Tamoxifen / Q000627:therapeutic use; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D013629:Tamoxifen; D014568:Urokinase-Type Plasminogen Activator