title: Prognostic relevance of uPAR-del4/5 and TIMP-3 mRNA expression levels in breast cancer.
abstract: Recently, two components of important protease systems in cancer, i.e., the urokinase plasminogen activator receptor (uPAR) mRNA splice variant uPAR-del4/5 and the tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), were independently reported to be of prognostic value in breast cancer. In the present study, we have evaluated the impact of both these factors on disease-free survival (DFS) in 205 breast cancer patients by assessing mRNA expression in tumour tissue by quantitative PCR. High uPAR-del4/5 mRNA expression was associated with shorter DFS in breast cancer patients (P=0.0363), whereas high TIMP-3 mRNA levels were associated with a good prognosis (P=0.0049). Furthermore, by combining uPAR-del4/5 with TIMP-3 values, we demonstrate that breast cancer patients with high uPAR-del4/5 and low TIMP-3 mRNA levels had a highly significantly shorter DFS in comparison to those patients with low uPAR-del4/5 and high TIMP-3 mRNA expression (P<0.0001). These patients had a more than 6-fold higher risk for disease recurrence or death in multivariate analysis. Therefore, considering the prognostic impact of two proteolytic factors stemming from complementary protease systems may improve the prediction of disease recurrence in breast cancer.
authors.affiliation: Institute of Pathology, Technical University Dresden, Fetscherstr. 74, D-01307 Dresden, Germany. matthias.kotzsch@uniklinikum-dresden.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Kotzsch
authors.forename: Juliane
authors.initials: J
authors.lastname: Farthmann
authors.forename: Axel
authors.initials: A
authors.lastname: Meye
authors.forename: Susanne
authors.initials: S
authors.lastname: Fuessel
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baretton
authors.forename: Vivianne C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmitt
authors.forename: Thomas
authors.initials: T
authors.lastname: Luther
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Viktor
authors.initials: V
authors.lastname: Magdolen
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D018076:DNA, Complementary / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019717:Tissue Inhibitor of Metalloproteinase-3