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.
Highlights
This study was performed on a group of 249 node-positive patients with operable primary breast cancer and without signs of distant meastasis at surgery
Selection of patients was made on the basis of the availability of tumour cytosol of the 394 node-positive patients included in the study reported previously (Foekens et al, 1992)
urokinase-type plainogen activator (UPA) antigen was measured by enzyme-linked immunosorbent assay, as described previously in detail (Foekens et al, 1992), using reagents of a kit which is commerially available
Summary
This study was performed on a group of 249 node-positive patients with operable primary breast cancer and without signs of distant meastasis at surgery. Selection of patients was made on the basis of the availability of tumour cytosol of the 394 node-positive patients included in the study reported previously (Foekens et al, 1992). For patients who underwent axillary surgery, histological emination was used to confirm the number of lymph nodes with tumour involnement. Postmenopausal women older than 55 years generally received no adjuvant therapy (133/164)
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