Impact of cyclins E, neutrophil elastase and proteinase 3 expression levels on clinical outcome in primary breast cancer patients†
Christine Desmedt
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Christine Desmedt and Frank El Ouriaghli are co-first authors.
Search for more papers by this authorFrank El Ouriaghli
Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Christine Desmedt and Frank El Ouriaghli are co-first authors.
Search for more papers by this authorVirginie Durbecq
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorAnne Soree
Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorMaria Antonetta Colozza
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorEvandro Azambuja
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorMarianne Paesmans
Data Centre, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorDenis Larsimont
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorMarc Buyse
International Drug Development Institute (IDDI), Brussels, Belgium
Search for more papers by this authorAdrian Harris
Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Molecular Angiogenesis Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Search for more papers by this authorMartine Piccart
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorPhilippe Martiat
Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorCorresponding Author
Christos Sotiriou
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Fax: +32-2-538-0858.
121 Boulevard de Waterloo, 1000 Brussels, BelgiumSearch for more papers by this authorChristine Desmedt
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Christine Desmedt and Frank El Ouriaghli are co-first authors.
Search for more papers by this authorFrank El Ouriaghli
Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Christine Desmedt and Frank El Ouriaghli are co-first authors.
Search for more papers by this authorVirginie Durbecq
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorAnne Soree
Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorMaria Antonetta Colozza
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorEvandro Azambuja
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorMarianne Paesmans
Data Centre, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorDenis Larsimont
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorMarc Buyse
International Drug Development Institute (IDDI), Brussels, Belgium
Search for more papers by this authorAdrian Harris
Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Molecular Angiogenesis Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Search for more papers by this authorMartine Piccart
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorPhilippe Martiat
Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorCorresponding Author
Christos Sotiriou
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Fax: +32-2-538-0858.
121 Boulevard de Waterloo, 1000 Brussels, BelgiumSearch for more papers by this authorThe authors declare that they have no competing interests.
Abstract
Uncontrolled cell proliferation is one of the hallmarks of cancer and the transition from the G1 to S phase is the most commonly reported cell cycle abnormality in tumors. It has been shown that the oncogenic activity of G1 cyclin E (CCNE) can be amplified by generating hyperactive low molecular weight forms (LMW) through elastase-mediated proteolytic processing. Neutrophil elastase (NE) and proteinase 3 (PR3) are 2 proteases that are aberrantly expressed in breast cancer cells and seem to be involved in cell proliferation. In this study, we evaluated the effect of the expression of these 2 proteases in addition to 2 potential intracellular targets of NE (CCNE1 and CCNE2) on clinical outcome in a population of 205 primary breast cancer patients. By univariate analysis, CCNE1, CCNE2, estrogen receptor and grade significantly predicted relapse free interval (RFI). NE and PR3 did not achieve statistical significance. In a multivariate analysis, elevated CCNE2 [hazard ratio (HR) 2.10, p = 0.008] predicted shorter RFI. In subgroup analyses of the tamoxifen-only treated patients, high CCNE1 levels predicted treatment resistance, while high levels of CCNE2 were associated with poor RFI in untreated patients. Investigation of the relationship between CCNE1, CCNE2 and NE did not show any impact on RFI. To conclude, this study was the first to evaluate these markers at the mRNA level by RT-PCR in a series of primary breast cancer patients, and our results confirmed the impact of high CCNE levels on clinical outcome in systemically untreated and of CCNE1 in tamoxifen-only treated early breast cancer patients. © 2006 Wiley-Liss, Inc.
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