Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer.
BACKGROUND
One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer.


METHODS
The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR.


RESULTS
uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value.


CONCLUSIONS
These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients.
Leissner
Philippe
P
Oncology & Human Genetics Department, bioMérieux SA, Grenoble, F-38024, France. Philippe.leissner@eu.biomerieux.com
Verjat
Thibault
T
Bachelot
Thomas
T
Paye
Malick
M
Krause
Alexander
A
Puisieux
Alain
A
Mougin
Bruno
B
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014568:Urokinase-Type Plasminogen Activator