TY - JOUR
T1 - Prognostic relevance of uPAR-del4/5 and TIMP-3 mRNA expression levels in breast cancer
AU - Kotzsch, Matthias
AU - Farthmann, Juliane
AU - Meye, Axel
AU - Fuessel, Susanne
AU - Baretton, Gustavo
AU - Tjan-Heijnen, Vivianne C.G.
AU - Schmitt, Manfred
AU - Luther, Thomas
AU - Sweep, Fred C.G.J.
AU - Magdolen, Viktor
AU - Span, Paul N.
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Prognosis
KW - Quantitative real-time PCR
KW - Tissue inhibitor of metalloproteinase-3
KW - Urokinase receptor transcript variants
UR - https://www.scopus.com/pages/publications/27744522730
U2 - 10.1016/j.ejca.2005.09.002
DO - 10.1016/j.ejca.2005.09.002
M3 - Article
C2 - 16256342
AN - SCOPUS:27744522730
SN - 0959-8049
VL - 41
SP - 2760
EP - 2768
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 17
ER -
