title: Tumour-associated fibrinolysis: the prognostic relevance of plasminogen activators uPA and tPA in human breast cancer.
abstract: Prognostic variables in breast cancer are urgently needed to individualize adjuvant cytotoxic therapy, especially in those patients where metastases in the lymph nodes have not been detected (node-negative disease). So far histomorphological criteria, the determination of receptors for steroid hormones or EGF (epidermal growth factor), the protease cathepsin D or DNA-ploidy are used to distinguish between low- and high-risk patients. High-risk patients have a higher incidence of recurrences and/or shorter overall survival after surgery of the primary tumour than low-risk patients. High-risk patients (node-positive; hormone-receptor-negative) would receive adjuvant hormone therapy or chemotherapy. In the node-negative patient, adjuvant therapy is only recommended if a high content of cathepsin D and aneuploidy of the tumour (or high S-phase in diploid tumours) has been diagnosed. Determination of cathepsin D in tumour extracts as a variable in breast cancer patients is based on the fact that invasion and metastasis is correlated with elevated levels of tumour-associated proteases such as cathepsins B and D, collagenase IV and plasminogen activators. The urokinase-type plasminogen activator (uPA) which is secreted by tumour cells as an enzymatically inactive proenzyme (pro-uPA) seems to play a key role in mediating tumour cell invasion in cancer tissues. Receptor-bound uPA converts enzymatically inactive plasminogen into the serine protease plasmin which then degrades the extracellular matrix surrounding the tumour cells (tumour stroma). We localized pro-uPA/uPA immunohistochemically in paraffin-embedded formalin-fixed breast cancer tissue sections. Pro-uPA/uPA was detected in the cytoplasm and on the plasma membrane of the tumour cells reflecting receptor-bound pro-uPA/uPA.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Frauenklinik der Technischen Universität München, Germany.
authors: M
authors: M
authors: Schmitt
authors: F
authors: F
authors: Jänicke
authors: H
authors: H
authors: Graeff
mesh_terms: D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality; D002402:Cathepsin D / Q000032:analysis; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008207:Lymphatic Metastasis; D009363:Neoplasm Proteins / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis; D010959:Tissue Plasminogen Activator / Q000032:analysis*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D002402:Cathepsin D