Cellular accumulation of uPA-PAI-1 [correction of UPA-PAI-1] and uPA-PAI-2 [correction of UPA-PAI-2] complexes in early (pT1) breast cancer: a new link in the uPA-UPAr-PAI chain.
OBJECTIVE
To investigate the role of uPA in early (pT1) breast cancer.


METHODS
Immunohistochemistry (streptavidin-biotin-peroxidase system), using the Chemicon AB776 polyclonal antibody, which reacts with uPA-PA-1 and uPA-PAI-2 complexes, was performed. In addition, CD44std, Ki67, c-erb-B2, p53, ER and PR expression were studied on the same tissue samples by the same method. The results obtained were correlated with nodal invasion, with each other and with classical pathologic features such as histologic and nuclear grade by means of the Spearman test for nonparametric variables.


RESULTS
The immunohistochemical reaction with uPA-PAI-1 and uPA-PAI-2 complexes was cytoplasmic and localized inside the tumor cells, with no, or only minimal reaction in the stromal cells. uPA-positivity detected by this method correlated significantly with ER expression (p = 0.031), PR expression (p = 0.030), favorable nuclear grade (p = 0.0087) and marginally with a low proliferation rate (p = 0.088), which was the opposite of the results reported by most other groups when studying either free uPA or uPA bound to its membrane receptor (uPAr) in similar tumors.


CONCLUSIONS
From our results we conclude that uPA-PAI-1 and uPA-PAI-2 complexes are formed inside the tumor cells for the purpose of inactivating free or uPAr-bound uPA, which explains why our findings were the reverse of those obtained when studying these latter forms. A model incorporating our data and the present knowledge on the uPA-uPAr-PAI chain is proposed.
Schneider
J
J
Fundación Tejerina-Centro de Patología de la Mama, Madrid, Spain. schneider@teleline.es
Lucas
R
R
Sánchez
J
J
Tejerina
A
A
Ruibal
A
A
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014568:Urokinase-Type Plasminogen Activator