Plasminogen activator inhibitor-2: prognostic relevance in 1012 patients with primary breast cancer.
The antigen levels of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor (PAI) 1, as detected in tumor extracts by ELISA, have been reported to be correlated with a poor prognosis in primary breast cancer. In the present study we have characterized a novel PAI-2-specific ELISA, designed to measure PAI-2 antigen levels in tumor cytosols. We determined PAI-2 antigen levels along with those of uPA and PAI-1 in 1012 routinely prepared tumor cytosols of patients with primary breast cancer (median follow-up, 71 months). In the overall population there was no significant association between the level of PAI-2 and prognosis, while in tumors with high uPA values, PAI-2 (test for trend) was associated with a prolonged relapse-free survival, metastasis-free survival, and overall survival (for all analyses, P < 0.02). In Cox's multivariate analysis for relapse-free survival, metastasis-free survival, and overall survival in tumors with high uPA values (including patient's age, menopausal status, lymph node status, tumor size, estrogen and progesterone receptor status, uPA, and PAI-1), PAI-2 either dichotomized or, as a continuous variable, was independently associated with a favorable relapse-free survival, metastasis-free survival, and overall survival. We conclude that the PAI-2-specific ELISA described herein is well suited for the measurement of PAI-2 levels in cytosols routinely prepared for analysis of steroid hormone receptors. We speculate that PAI-2 may serve as an inhibitor for uPA in human primary breast cancers.
Foekens
J A
JA
Division of Endocrine Oncology (Department of Medical Oncology), Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Buessecker
F
F
Peters
H A
HA
Krainick
U
U
van Putten
W L
WL
Look
M P
MP
Klijn
J G
JG
Kramer
M D
MD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality; D003600:Cytosol / Q000737:chemistry; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis*; D012044:Regression Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D017396:Plasminogen Activator Inhibitor 2; D014568:Urokinase-Type Plasminogen Activator