Impact of cyclins E, neutrophil elastase and proteinase 3 expression levels on clinical outcome in primary breast cancer patients.
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.
Desmedt
Christine
C
Translational Research Unit, Department of Medical Oncology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.
Ouriaghli
Frank El
FE
Durbecq
Virginie
V
Soree
Anne
A
Colozza
Maria Antonetta
MA
Azambuja
Evandro
E
Paesmans
Marianne
M
Larsimont
Denis
D
Buyse
Marc
M
Harris
Adrian
A
Piccart
Martine
M
Martiat
Philippe
P
Sotiriou
Christos
C
D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000628:therapy; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D053146:Myeloblastin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D019927:Cyclin E; D017931:DNA Primers; D012333:RNA, Messenger; D019272:Leukocyte Elastase; D053146:Myeloblastin