title: Karyopherin a2 and chromosome region maintenance protein 1 expression in meningiomas: novel biomarkers for recurrence and malignant progression.
abstract: The karyopherin protein family comprises importins and exportins which are nucleocytoplasmic shuttling receptors. Increased levels of karyopherin a2 and chromosome region maintenance protein 1 correlate with a higher WHO grade and a poorer prognosis in patients with infiltrative astrocytomas. The aim of this study was to evaluate representative members of importins and exportins (i.e. karyopherin a2 and chromosome region maintenance protein 1) as novel biomarkers for meningiomas of WHO grades I-III. We semiquantitatively analyzed nuclear expression of karyopherin a2, chromosome region maintenance protein 1 and the MIB1 labeling index using immunohistochemistry in 108 primary (44 meningiomas WHO grade I, 48 meningiomas WHO grade II, 16 meningiomas WHO grade III) and 13 recurrent meningiomas. Statistical analysis was performed using standard techniques. Karyopherin a2 (p < 0.001) and chromosome region maintenance protein 1 (p = 0.002) expression correlated significantly with the histological grade. Karyopherin a2 expression correlated with proliferative activity as assessed by the MIB1 index (p < 0.001). Recurrent tumors expressed significantly higher levels of karyopherin a2 (p = 0.045) when compared to primary growths. Multivariate analysis of the overall series as well as of patients with atypical meningiomas identified higher karyopherin a2 (≥ 5 vs. <5%) and chromosome region maintenance protein 1 (≥ 60 vs. 60%) expression as independent predictors of tumor recurrence. Karyopherin a2 and chromosome region maintenance protein 1 expression may have potential as novel biomarkers for meningiomas.
authors.affiliation: Department of Neurosurgery, University Hospital of Bonn, Sigmund Freud Strasse 25, 53105, Bonn, Germany. kostasgousias@yahoo.com.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Gousias
authors.affiliation: Department of Neuropathology, University Hospital of Bonn, Sigmund Freud Strasse 25, 53105, Bonn, Germany.
authors.forename: Pitt
authors.initials: P
authors.lastname: Niehusmann
authors.affiliation: Department of Neuropathology, University Hospital of Bonn, Sigmund Freud Strasse 25, 53105, Bonn, Germany.
authors.forename: Gerrit H
authors.initials: GH
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
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D028884:Karyopherins / Q000378:metabolism*; D008297:Male; D008577:Meningeal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008579:Meningioma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism; D011379:Prognosis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D019292:Skull Base Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D028901:alpha Karyopherins / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D015415:Biomarkers; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D028901:alpha Karyopherins; D000097606:Exportin 1 Protein; C490630:KPNA2 protein, human