title: KPNA2 predicts long term survival in patients with anaplastic oligoastrocytomas.
abstract: The family of karyopherins comprises importins and exportins which are both involved in nucleocytoplasmic shuttling. Increased levels of karyopherin a2/importin 1 (KPNA2) and chromosome region maintenance protein 1/exportin 1 (CRM1) have been associated with poorer prognosis in patients with infiltrative astrocytomas. Isocitrate dehydrogenase 1 gene (IDH1) R132H mutation status was also recently identified as a prognostic factor for malignant gliomas. We evaluated KPNA2 and CRM1, as well as the IDH1 mutation status, as possible novel biomarkers for World Health Organization grade III anaplastic oligoastrocytomas (AOA). We analyzed nuclear expression of KPNA2 by immunohistochemistry in 72 primary anaplastic gliomas (29 AOA, 24 anaplastic astrocytomas, 19 anaplastic oligodendrogliomas). The IDH1 mutation status was also determined in patients with anaplastic astrocytomas and AOA, and AOA patients were additionally evaluated for CRM1 nuclear expression. Long term survivors (LTS; >8 years) with AOA showed lower KPNA2 expression levels compared to non-LTS (p=0.005). KPNA2 expression (⩾ 5% versus <5%, 1-<5%, median) was found to correlate inversely with overall survival (OS) and progression-free survival (PFS) in our overall series as well as in the AOA group (anaplastic gliomas: OS p=0.017; PFS p=0.033; AOA: OS p=0.017, PFS p=0.040). Mutant IDH1-R132H was detected in 69% of the AOA cohort; a combination of KPNA2 low expression and mutant IDH1-R132H was only seen in LTS (p=0.050). No differences between the histological subtypes were observed in terms of KPNA2 expression and IDH1-R132H mutation status. To our knowledge this is the first time it has been shown that KPNA2 expression may have potential as a prognostic biomarker for AOA as well.
authors.affiliation: Department of Neurosurgery, University Hospital of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany. Electronic address: kostasgousias@yahoo.com.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Gousias
authors.affiliation: Department of Neuropathology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Pitt
authors.initials: P
authors.lastname: Niehusmann
authors.affiliation: Department of Neuropathology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Gielen
authors.affiliation: Department of Neurosurgery, University Hospital of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.affiliation: Department of Neurosurgery, University Hospital of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany; Department of Radiosurgery and Stereotactic Radiotherapy, MediClin Robert Janker Clinic, Bonn, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Boström
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D028884:Karyopherins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D028901:alpha Karyopherins / Q000235:genetics* / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D015415:Biomarkers; D007521:Isocitrate Dehydrogenase; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D028901:alpha Karyopherins; D000097606:Exportin 1 Protein; C087978:karyopherin alpha 2; C543588:IDH1 protein, human
keywords: Anaplastic oligoastrocytomas; Chromosome region maintenance protein 1/exportin 1; IDH1-R132H mutation status; Karyopherin a2/importin 1