1. ¹GSF-National Research Center for Environment and Health, Institute of Pathology, D-85764 Neuherberg, Germany
2. ²Technical University of Munich, Institute of Pathology, Trogerstr. 18, 81675 München, Germany
3. ³Department of Oncology and Pathology, Karolinska Institute and Hospital, S-17176, Stockholm, Sweden
4. ⁴Institute of Pathology, Universitätsklinikum Freiburg, Breisacher Strae 115a, 79106 Freiburg I., Br., Germany
5. ⁵Endocrine Cancer Group, Cancer Research Centre, Western General Hospital, Crewe Road, EH4 2XR, South Edinburgh, UK
6. ⁶GSF-National Research Center for Environment and Health, Institute of Molecular Radiation Biology, D-85764, Neuherberg, Germany

Correspondence: Dr M Aubele, GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Pathologie, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. E-mail: aubele@gsf.de

Received 30 October 2006; Revised 3 January 2007; Accepted 9 January 2007; Published online 13 February 2007.

Abstract

The HER receptors are of therapeutic and prognostic significance in breast cancer, and their function is modulated by cytoplasmic tyrosine kinases like PTK6 (brk). We performed a retrospective study on archival breast cancer samples from patients with long follow-up and compared the protein expression between individual HERs and between HERs and the PTK6. Univariate and multivariate analyses were used to study the prognostic value of parameters. Metastases-free survival of patients for longer than 240 months was inversely associated (P0.05) with nodal status, tumour size, and oestrogen receptor status, but was also directly associated with high protein expression levels of HER4 and PTK6 in Kaplan–Meier analysis. In multivariate analysis for metastases-free survival of >240 months, the stepwise selected parameters were tumour size (relative risk 3.1), PTK6 expression (0.4), and number of positive lymph nodes (1.2). Furthermore, we demonstrated a timedependence of the prognostic value attributed to the parameters. The HER receptors (HER2,4), but not PTK6, were independent prognostic markers for metastases-free survival at 60 months, whereas at 240 months PTK6 is the strongest prognostic marker. We demonstrate that PTK6 is a prognostic marker of metastases-free survival in breast cancer, and is independent of the classical morphological and molecular markers of lymph node involvement, tumour size, and HER2 status.