title: Protein expression of BIRC5, TK1, and TOP2A in malignant peripheral nerve sheath tumours--A prognostic test after surgical resection.
abstract: No consensus treatment regime exists beyond surgery for malignant peripheral nerve sheath tumours (MPNST), and the purpose of the present study was to find new approaches to stratify patients with good and poor prognosis and to better guide therapeutic intervention for this aggressive soft tissue cancer. From a total of 67 MPNSTs from Scandinavian patients with and without neurofibromatosis type 1, 30 MPNSTs were investigated by genome-wide RNA expression profiling and 63 MPNSTs by immunohistochemical (IHC) analysis, and selected genes were submitted to analyses of disease-specific survival. The potential drug target genes survivin (BIRC5), thymidine kinase 1 (TK1), and topoisomerase 2-alpha (TOP2A), all encoded on chromosome arm 17q, were up-regulated in MPNST as compared to benign neurofibromas. Each of them was found to be independent prognostic markers on the gene expression level, as well as on the protein level. A prognostic profile was identified by combining the nuclear expression scores of the three proteins. For patients with completely resected tumours only 15% in the high risk group were alive after two years, as compared to 78% in the low risk group. In conclusion, we found a novel protein expression profile which identifies MPNST patients with inferior prognosis even after assumed curative surgery. The tested proteins are drug targets; therefore the expression profile may provide predictive information guiding the design of future clinical trials. Importantly, as the effect is seen on the protein level using IHC, the biomarker panel can be readily implemented in routine clinical testing.
authors.affiliation: Department of Molecular Oncology, Institute for Cancer Research, Division of Cancer Medicine Surgery and Transplantation, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kolberg
authors.affiliation: Department of Molecular Oncology, Institute for Cancer Research, Division of Cancer Medicine Surgery and Transplantation, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
authors.forename: Maren
authors.initials: M
authors.lastname: Høland
authors.affiliation: Department of Molecular Oncology, Institute for Cancer Research, Division of Cancer Medicine Surgery and Transplantation, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
authors.forename: Guro E
authors.initials: GE
authors.lastname: Lind
authors.affiliation: Department of Molecular Oncology, Institute for Cancer Research, Division of Cancer Medicine Surgery and Transplantation, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Trude H
authors.initials: TH
authors.lastname: Ågesen
authors.affiliation: Department of Molecular Oncology, Institute for Cancer Research, Division of Cancer Medicine Surgery and Transplantation, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Rolf I
authors.initials: RI
authors.lastname: Skotheim
authors.affiliation: Department of Oncology, Division of Cancer Medicine Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Kirsten Sundby
authors.initials: KS
authors.lastname: Hall
authors.affiliation: Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Oncology, Division of Cancer Medicine Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Smeland
authors.affiliation: Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Pathology, Division of Diagnostics and Intervention, Oslo University Hospital, Oslo, Norway.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.affiliation: Department of Molecular Oncology, Institute for Cancer Research, Division of Cancer Medicine Surgery and Transplantation, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway. Electronic address: rlothe@rr-research.no.
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009442:Neurilemmoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000075223:Poly-ADP-Ribose Binding Proteins; D012189:Retrospective Studies; D015996:Survival Rate; D000077022:Survivin; D013937:Thymidine Kinase / Q000096:biosynthesis*
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000077022:Survivin; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human
keywords: BIRC5; Immunohistochemistry; MPNST; Prognosis; Survivin; TK1; TOP2A