Prognostic significance of tumor-related proteases as a function of the estrogen receptor status.
BACKGROUND
Tumor-related proteases such as urokinase-type plasminogen (uPA), plasminogen activator inhibitor (PAI-1), and cathepsin D (cath-D) are involved in the prognosis of breast cancer (BC) and promote the metastatic process. We investigated the relationship between these proteases and their prognostic significance according to the ER status.


METHODS
uPA, PAI-1, and cath-D levels were prospectively measured in tumor from 316 patients with primary BC. The distribution and relationship between these proteases and ER subsets were analyzed as well as the prognostic significance.


RESULTS
Quantitative levels of uPA, and PAI-1 were higher in ER-patients (p< 0.001) whereas no difference was observed for cath-D levels in ER subsets (p = 0.96). In patients with a positive and highly positive ER status, a high cath-D level was associated with a poorer prognosis. Patients in the highly positive ER group experienced poorer survival in the group with a high PAI-1 level compared to the group with a low PAI-1 level. In ER+ patients, cath-D (p= 0.02) and the tumor size (p= 0.03) were independent factors for OS.


CONCLUSIONS
The prognostic significance of proteases is modulated by the ER status. Cath-D and PAI-1 could identify a high-risk group with an adverse outcome in ER+ patients.
Department de chirurgie generale, IGR, Villejuif, France. chafika.mazouni@igr.fr
Chafika
C
Mazouni
Sylvie
S
Romain
Pascal
P
Bonnier
L'Houcine
L
Ouafik
Pierre-Marie
PM
Martin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D002402:Cathepsin D / Q000032:analysis; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D010447:Peptide Hydrolases / Q000032:analysis*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D017395:Plasminogen Activator Inhibitor 1; D011960:Receptors, Estrogen; D010447:Peptide Hydrolases; D014568:Urokinase-Type Plasminogen Activator; D002402:Cathepsin D