Author(s):
|
Dorssers, L.C.;
Grebenchtchikov, N.J.
;
Brinkman, A.B.
; Look, M.P.; Broekhoven, S.P. van;
Jong, D. de
;
Peters, H.A.
; Portengen, H.; Meijer-van Gelder, M.E.; Klijn, J.G.M.;
Tienoven, T.H. van
;
Geurts-Moespot, A.
;
Span, P.N.
; Foekens, J.A.;
Sweep, C.G.J.
|
Subject:
|
UMCN 5.2: Endocrinology and reproduction |
Organization:
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Chemical Endocrinology Molecular Biology Neurology Laboratory of Genetic, Endocrine and Metabolic Diseases |
Former Organization:
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Radboud University Nijmegen Medical Centre
|
Abstract:
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PURPOSE: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large series of breast cancer specimens. EXPERIMENTAL DESIGN: A specific ELISA was developed to measure BCAR1 protein levels in 2593 primary breast tumor cytosols. Tumor levels of BCAR1 were correlated with relapse-free survival (RFS) and overall survival (OS) and compared with collected data on urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1). RESULTS: In tumor cytosols, BCAR1 protein levels varied between 0.02 and 23 ng/mg protein. BCAR1 levels exhibited a positive correlation with steroid hormone receptor levels, age and menopausal status, and uPA and PAI-1 levels. The level of BCAR1 (continuous or categorized as low, intermediate, or high) was inversely related with RFS and OS time. Multivariate analysis showed that BCAR1 levels contributed independently to a base model containing the traditional prognostic factors for both RFS and OS (both P < 0.0001). When added together with uPA and PAI-1 in the multivariate model, BCAR1 contributed independently of PAI-1 and was favored over uPA. Interaction tests allowed for additional analyses of BCAR1 protein levels in clinically relevant subgroups stratified by nodal and menopausal status. CONCLUSIONS: The quantitative BCAR1 protein level represents a prognostic factor for RFS and OS in primary breast cancer, independent of the traditional prognostic factors and the other novel marker PAI-1.
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