A prospective study on the prognostic significance of urokinase-type plasminogen activator levels in breast cancer tissue.
Urokinase-type plasminogen activator (u-PA), which cleaves plasminogen to yield plasmin, is a serine protease of fibrinolysis and is presumed to play a key role in extracellular proteolysis and facilitate the migration of cancer cells. This study was conducted prospectively to evaluate the prognostic significance of u-PA antigen level in breast cancer tissues. u-PA concentrations in the cytosol of 226 breast cancer tissues were determined prospectively by enzyme-linked immunosorbent assay using cytosol fractions prepared for steroid hormone assay. The median follow-up period of the patients was 60 months. Various prognostic factors were evaluated by univariate analysis or multivariate analysis using the Cox proportional-hazards method. Patients with primary breast cancer containing high levels of u-PA had a significantly shorter disease-free survival than patients with low levels of u-PA antigens. In multivariate analysis, a high level of u-PA was an independent risk factor for disease-free survival, being independent of age, axillary node status, and estrogen receptor status. Among the major prognostic factors, a high u-PA antigen level, lymph node involvement, and a positive estrogen receptor status were the most important for predicting relapse-free survival (P = 0.044, P < 0.0001, P = 0.0039). This first prospective study confirmed the prognostic significance of the u-PA antigen level in association with other major prognostic factors. The results of our present study suggest that u-PA in breast cancer tissue might be involved in breast cancer invasion and metastasis.
Shiba
E
E
Department of Surgical Oncology, Osaka University Medical School, Japan.
Kim
S J
SJ
Taguchi
T
T
Izukura
M
M
Kobayashi
T
T
Furukawa
J
J
Yayoi
E
E
Shin
E
E
Takatsuka
Y
Y
Koyama
H
H
Takai
S
S
D000367:Age Factors; D001943:Breast Neoplasms / Q000201:enzymology*; D003600:Cytosol / Q000201:enzymology; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012044:Regression Analysis; D012306:Risk; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014568:Urokinase-Type Plasminogen Activator