title: The Sub-Cellular Localization of WRAP53 Has Prognostic Impact in Breast Cancer.
abstract: WRAP53 protein controls intracellular trafficking of DNA repair proteins, the telomerase enzyme, and splicing factors. Functional loss of the protein has been linked to carcinogenesis, premature aging and neurodegeneration. The aim of this study was to investigate the prognostic significance of WRAP53 protein expression in breast cancer. A tissue microarray was constructed from primary breast tumors and immunostained by a polyclonal WRAP53 antibody to assess the protein expression pattern. Two different patient cohorts with long term follow-up were studied; a test- and a validation set of 154 and 668 breast tumor samples respectively. Breast cancer patients with tumor cells lacking the expression of WRAP53 in the nucleus had a significantly poorer outcome compared to patients with tumor cells expressing this protein in the nuclei (HR = 1.95, 95%CI = 1.09-3.51, p = 0.025). Nuclear localization of WRAP53 was further shown to be an independent marker of prognosis in multivariate analysis (HR = 2.57, 95%CI = 1.27-5.19, p = 0.008), and also significantly associated with better outcome in patients with TP53 mutation. Here we show that the sub-cellular localization of the WRAP53 protein has a significant impact on breast cancer survival, and thus has a potential as a clinical marker in diagnostics and treatment.
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Radiumhospitalet-Oslo University Hospital, 0424 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0313 Oslo, Norway.
authors.forename: Laxmi
authors.initials: L
authors.lastname: Silwal-Pandit
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Radiumhospitalet-Oslo University Hospital, 0424 Oslo, Norway; Department of Pathology, Division of Diagnostics and Intervention, Oslo University Hospital, 0450 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0313 Oslo, Norway.
authors.forename: Hege
authors.initials: H
authors.lastname: Russnes
authors.affiliation: Department of Pathology, Division of Diagnostics and Intervention, Oslo University Hospital, 0450 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0313 Oslo, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Borgen
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Radiumhospitalet-Oslo University Hospital, 0424 Oslo, Norway.
authors.forename: Veronica
authors.initials: V
authors.lastname: Skarpeteig
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Radiumhospitalet-Oslo University Hospital, 0424 Oslo, Norway; Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital, 0450 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0313 Oslo, Norway.
authors.forename: Hans Kristian
authors.initials: HK
authors.lastname: Moen Vollan
authors.affiliation: Department of Breast- and Endocrine Surgery, Division of Surgery, Cancer and Transplantation, Oslo University Hospital, 0450 Oslo, Norway.
authors.forename: Ellen
authors.initials: E
authors.lastname: Schlichting
authors.affiliation: K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0313 Oslo, Norway; Department of Breast- and Endocrine Surgery, Division of Surgery, Cancer and Transplantation, Oslo University Hospital, 0450 Oslo, Norway.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kåresen
authors.affiliation: Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital, 0450 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0313 Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Radiumhospitalet-Oslo University Hospital, 0424 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0313 Oslo, Norway.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.affiliation: Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, SE-17176 Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Farnebo
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Radiumhospitalet-Oslo University Hospital, 0424 Oslo, Norway.
authors.forename: Anita
authors.initials: A
authors.lastname: Langerød
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D018832:Molecular Chaperones; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D021381:Protein Transport; D013347:Subcellular Fractions; D019098:Telomerase / Q000378:metabolism*
chemical_list: D018832:Molecular Chaperones; D019098:Telomerase; C535133:WRAP53 protein, human