Plasminogen activator inhibitor type 1 is the most significant of the usual tissue prognostic factors in node-negative breast ductal adenocarcinoma independent of urokinase-type plasminogen activator.
OBJECTIVE
The aim of the present investigation was to evaluate the prognostic significance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) tissue contents in primary breast adenocarcinoma.


METHODS
Patients from 3 medical centers were included between 1994 and 2001. Biologic factors in tumor extracts were all assayed in the same laboratory. PAI-1 and uPA were treated as continuous or dichotomized variables. Metastasis-free survival analyses were performed using the Cox model and the classification algorithm and regression tree (CART) in the whole population and in the subsets of node-negative (pN0) or positive (pN+) cases. Kaplan curves of metastasis-free survival were designed for different groups in relation to uPA/PAI-1 combinations. Urokinase-type plasminogen activator tumor level appears related to the anatomic degree of extension; conversely, PAI-1 tumor content is independent of tumor size and nodal extension.


RESULTS
In univariate analysis, adjusted on usual prognostic factors, the metastasis risk increased with PAI-1 level in all patients (HR [hazard ratio], 3.1; P < .001), in pN0 (HR, 4.3; P < .001), and pN+ patients (HR, 2.3; P = .019). It increased also with uPA in all patients (HR, 2.6; P = 0.006). In multivariate analysis, when both variables were included, PAI-1 remained significant in all patients (HR, 2.4; P = .002) and pN0 patients (HR, 3.2; P = .003) but not uPA. CART analyses confirmed that the best partitioning factor was PAI-1.


CONCLUSIONS
There was no evidence for any additional impact of uPA. PAI-1 is an independent prognostic factor in particular in pN0 breast ductal carcinoma.
Descotes
Françoise
F
Service de Biologie des Tumeurs Solides, Centre Hospitalier Universitaire Lyon-Sud, Pierre Benite, France. francoise.descotes@chu-lyon.fr
Riche
Benjamin
B
Saez
Simone
S
De Laroche
Guy
G
Datchary
Jean
J
Roy
Pascal
P
André
Jean
J
Bobin
Jean Yves
JY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011379:Prognosis; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator