Prognostic value of cytosolic tyrosine kinase activity in 249 node-positive breast cancer patients. |
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Authors: | S Romain O Chinot J G Klijn W L van Putten O Guirou M Look P M Martin and J A Foekens |
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Institution: | Laboratoire d''Oncologie Biologique, APM, Faculté de Médecine Nord, Marseille, France. |
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Abstract: | Tyrosine-specific protein kinase (TPK) has been associated with the cytoplasmic domain of growth factor receptors as well as oncoproteins. Enzymatic activation appears to be a major initial event in these signal transduction pathways. In this study, TPK was determined in the cytosols of 249 node-positive primary breast tumours. Enzyme activity was measured using 32P]ATP and poly(glutamic acid-tyrosine) (4:1) as an artificial substrate. Levels of TPK varied from 0 to 35.9 pmol ATP min-1 mg-1 protein (median 11.4). No correlation was found with tumour size or number of positive lymph nodes. In contrast, levels of TPK were negatively associated with age (P = 0.01) and menopausal status (P < 0.05) of the patients. Higher concentrations of TPK were in addition found in tumours negative for oestradiol (P < 0.01) and progesterone (P < 0.05) receptors. Finally, a positive correlation was found between TPK and urokinase plasminogen activator (UPA) (P < 0.05). Patients whose tumours contained high levels of TPK had reduced disease-free (P = 0.01) and overall survival (P < 0.05). In Cox multivariate analysis, including patient''s age, menopausal status, tumour size, number of positive lymph nodes, steroid receptors and UPA, TPK retained its independent prognostic importance. |
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