Prognostic value of cytosolic tyrosine kinase activity in 249 node-positive breast cancer patients.
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.
Romain
S
S
Laboratoire d'Oncologie Biologique, APM, Faculté de Médecine Nord, Marseille, France.
Chinot
O
O
Klijn
J G
JG
van Putten
W L
WL
Guirou
O
O
Look
M
M
Martin
P M
PM
Foekens
J A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D003600:Cytosol / Q000201:enzymology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D011505:Protein-Tyrosine Kinases