Clinical relevance of urokinase-type plasminogen activator, its receptor, and its inhibitor type 1 in endometrial cancer.
OBJECTIVE
Tumor invasion involves degradation of extracellular matrix. The urokinase plasminogen activation system participates in this process. Urokinase-type plasminogen activator (uPA), its receptor (uPAR), and its inhibitor, plasminogen activator inhibitor type 1 (PAI-1), are proposed to be prognostic factors in some cancers. There are conflicting data regarding the prognostic role of this system in endometrial cancer.


METHODS
To determine the prognostic value of the urokinase plasminogen activation system, contents of uPA, uPAR, and PAI-1 were measured in extracts of endometrial cancer tissue using ELISAs. uPA, uPAR, and PAI-1 levels were determined in 91, 54, and 92 extracts, respectively, and correlated with tumor histology, stage, grade, lymph node involvement, prevalence of metastasis, and recurrence as well as with estrogen (ER), progesterone (PR), epidermal growth factor (EGFR) receptor and HER-2/neu contents.


RESULTS
Patients with cancers exhibiting advanced stage, high grade, unfavorable tumor histology, nodal involvement, recurrence, and lower PR levels determined by ligand binding had significantly higher uPA content than others. PAI-1 was significantly elevated in patients with advanced stage, high-grade tumor, recurrence, decreased ER content, and lower PR levels determined by ligand binding. uPAR did not show any relation to any of clinical and laboratory parameters. Elevated expression of PAI-1 was associated with significantly shorter disease-free (P = 0.005) and overall (P = 0.0003) survival. Multivariate analysis revealed that PAI-1 was a predictor of survival although stage was the strongest independent factor.


CONCLUSIONS
Elevated uPA and PAI-1 levels appear to correlate with unfavorable prognosis in endometrial cancer.
Tecimer
C
C
Hormone Receptor Laboratory, University of Louisville, Louisville, Kentucky 40202, USA. tctecimer@ixir.com
Doering
D L
DL
Goldsmith
L J
LJ
Meyer
J S
JS
Abdulhay
G
G
Wittliff
J L
JL
D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013379:Substrate Specificity; D015996:Survival Rate; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D066246:ErbB Receptors; D017395:Plasminogen Activator Inhibitor 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; C524898:PLAUR protein, human