title: PTK (protein tyrosine kinase)-6 and HER2 and 4, but not HER1 and 3 predict long-term survival in breast carcinomas.
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 (P< or =0.05) 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.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute of Pathology, D-85764 Neuherberg, Germany. aubele@gsf.de
authors.forename: M
authors.initials: M
authors.lastname: Aubele
authors.forename: G
authors.initials: G
authors.lastname: Auer
authors.forename: A K
authors.initials: AK
authors.lastname: Walch
authors.forename: A
authors.initials: A
authors.lastname: Munro
authors.forename: M J
authors.initials: MJ
authors.lastname: Atkinson
authors.forename: H
authors.initials: H
authors.lastname: Braselmann
authors.forename: T
authors.initials: T
authors.lastname: Fornander
authors.forename: J M S
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D020893:Receptor, ErbB-3 / Q000096:biosynthesis; D066247:Receptor, ErbB-4; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C512478:EGFR protein, human; C587689:ERBB4 protein, human