PROTEIN-TYROSINE KINASE-ACTIVITY IN 350 T1 T2, N0/N1 BREAST-CANCER - PRELIMINARY-RESULTS/

Protein tyrosine kinases (PTKs) are a family of enzymes sharing a high ly conserved catalytic domain which phosphorylates substrate proteins on tyrosine residues. PTKs play a major role in the transduction of th e mitogenic signal and are involved in the control of cell proliferati on, differentiation, and transformation processes. PTKs can be subdivi ded into two major types: membrane associated PTKs consisting essentia lly of growth factor receptors (receptor tyrosine kinases or RTKs) and cytosolic PTKs involved in the intracellular transduction of mitogeni c and differentiation signals. From January 1988 to January 1992, PTK activity was assayed in cytosolic fractions prepared from 350 T1-T2, N 0-N1 M0, breast carcinomas. Enzymatic activity was measured using phos phate transfer from [P-32]-ATP to poly-Glu-Sr as an artificial substra te. According to our previously reported pilot study, we chose a cut-o ff value of 12 pmol P-32 incorporated min(-1) mg(-1) protein, correspo nding to the median value. We found positive PTK levels (greater than or equal to 12 pmol/min/mg) to be correlated with a loss of differenti ation according to Scarff-Bloom grade (p < 0.001), negative PR (p = 0. 03) and ER status (p = 0.04). With a median follow-up of 30 months (0- 82), patients with a positive PTK level presented a smaller 3-year dis ease free survival than in the PTK negative group of patients (p = 0.0 7). In Cox multivariate analysis including pT, pN, Scarff-Bloom grade, PR and ER, PTK activity does not emerge as a significant prognostic f actor.