Prognostic assessment of PTK activity in T1-T2, N0-N1, M0 breast cancer: a multicentric retrospective study

Abstract

Protein tyrosine kinases (PTKs) play a major role in the transduction of intracellular mitogenic signal. PTKs are also involved in the process of cellular transformation. A number of studies have reported increased PTK activities in cytosolic fractions from human breast carcinoma. However, the possible pronostic value of these activities is difficult to establish from these studies, mostly conducted on limited numbers of patients. In order to clear up the issue, we have investigated a large series of patients with a long follow-up, using a retrospective multicentric study (894 breast cancers T1-T2, N0-N1, M0; median follow-up: 67 months). PTKs were measured using a radioenzymatic assay as described in our previously report. We confirmed the already observed correlation between PTK activities and Scarff-Bloom grading (p < 10(-5)), negative estrogen receptor (ER), and progesterone receptor (PR) status. By contrast, we found in this study a correlation between PTK values and clinical nodal status (p = 0.00027) not showed in our precedent analysis. In Cox multivariate analysis, PTK activity does not emerge as a significant pronostic parameter. On the other hand, tumor PTK activity assay may prove of great interest in clinical research using newly developed tyrosine kinase inhibitors in order to assess their biological impact and eventually to predict the responsiveness to these new therapeutic agents.