PROGNOSTIC VALUE OF CYTOSOLIC TYROSINE KINASE-ACTIVITY IN 249 NODE-POSITIVE BREAST-CANCER PATIENTS

Tyrosine-specific protein kinase (TPK) has been associated with the cy toplasmic domain of growth factor receptors as well as oncoproteins. E nzymatic activation appears to be a major initial event in these signa l transduction pathways. In this study, TPK was determined in the cyto sols of 249 node-positive primary breast rumours. Enzyme activity was measured using [P-32]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 tumou r size or number of positive lymph nodes. In contrast, levels of TPK w ere negatively associated with age (P=0.01) and menopausal status (P<0 .05) of the patients. Higher concentrations of TPK were in addition fo und in tumours negative for oestradiol (P<0.01) and progesterone (P<0. 05) receptors. Finally, a positive correlation was found between TPK a nd urokinase plasminogen activator (UPA) (P<0.05). Patients whose tumo urs contained high levels of TPK had reduced disease-free (P = 0.01) a nd overall survival (P<0.05). In Cox multivariate analysis, including patient's age, menopausal status, tumour size, number of positive lymp h nodes, steroid receptors and UPA, TPK retained its independent progn ostic importance.