title: Tissue-type plasminogen activator (tPA) in breast cancer: relationship with clinicopathological parameters and prognostic significance.
abstract: BACKGROUND
  Tissue-type plasminogen activator (tPA) is a serine protease primarily involved in the intravascular dissolution of blood clots. High intratumoral tPA levels are associated with prognosis in several human tumors. In addition, tPA has been shown to be an estrogen-inducible protein in human breast cancer cell lines. The aim of the present study was to analyze the cytosolic tPA content in primary breast carcinomas and its potential clinical value.
  
  
  METHODS
  tPA was measured by a solid-phase enzyme immunoassay in tumor cytosol samples obtained from 800 patients with breast cancer. The median follow-up period was of 49.2 months.
  
  
  RESULTS
  Cytosolic tPA levels ranged widely in breast carcinomas (median: 3.9; range: 0.1- 315.3 ng/mg protein). tPA levels were significantly lower in large tumors, as well as in those showing poor differentiation, estrogen (ER) or PgR-negativity, aneuploidy, or a high S-phase fraction. In addition, low tPA intratumoral levels were associated with a high probability of both shortened relapse-free and overall survival in all patients and in the subgroup with node-negative tumors. However, our results did not show any significant relationship between intratumoral tPA levels and prognosis in the different subgroups of patients, stratified according to the type of systemic adjuvant therapy received (chemotherapy, tamoxifen or chemotherapy plus sequential tamoxifen).
  
  
  CONCLUSIONS
  The results of the present investigation indicate that low intratumoral tPA levels are associated with aggressiveness and poor prognosis in breast cancer patients. However, the study suggests that tPA levels do not predict response to systemic adjuvant therapy.
authors.affiliation: Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
authors.forename: M Daniela
authors.initials: MD
authors.lastname: Corte
authors.forename: Paula
authors.initials: P
authors.lastname: Vérez
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Rodríguez
authors.forename: Antonio
authors.initials: A
authors.lastname: Roibás
authors.forename: M Luz
authors.initials: ML
authors.lastname: Domínguez
authors.forename: M Luz
authors.initials: ML
authors.lastname: Lamelas
authors.forename: Julio
authors.initials: J
authors.lastname: Vázquez
authors.forename: José L
authors.initials: JL
authors.lastname: García Muñiz
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Allende
authors.forename: Luis Ovidio
authors.initials: LO
authors.lastname: González
authors.forename: Antonio
authors.initials: A
authors.lastname: Fueyo
authors.forename: Francisco
authors.initials: F
authors.lastname: Vizoso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003600:Cytosol / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D013030:Spain / Q000453:epidemiology; D018709:Statistics, Nonparametric; D015996:Survival Rate; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D010959:Tissue Plasminogen Activator