KPNA2 predicts long term survival in patients with anaplastic oligoastrocytomas |
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| Institution: | 1. Department of Neurosurgery, University Hospital of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany;2. Department of Neuropathology, University Hospital of Bonn, Bonn, Germany;3. Department of Radiosurgery and Stereotactic Radiotherapy, MediClin Robert Janker Clinic, Bonn, Germany;1. Neurosurgery Department, The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerley, Liverpool, L9 7LJ, UK;2. School of Medicine, University of Liverpool, Liverpool, UK;3. Department of Medicine and Medical Mycology, University Hospital of South Manchester, Manchester, UK;4. Microbiology Department, Aintree University Hospital NHS Foundation, Liverpool, UK;5. Otolaryngology Department, The Shrewsbury and Telford Hospital NHS Trust, Shrewsbury, UK;6. Otolaryngology Department, Aintree University Hospital NHS Foundation, Liverpool, UK;7. Neurosurgery Department, Beaumont Hospital, Dublin, Ireland;1. Department of Neurological Surgery, The Charles Clore Hospitalization Tower, West Wing Sheba Medical Center, Ramat Gan, Israel;2. Department of Pathology, Microbiology, and Immunology, 6439 Garners Ferry Rd., Building 1, Room C27, Columbia, SC 29209, USA;1. Department of General Anesthesiology, Anesthesiology Institute, Cleveland Clinic, 9500 Euclid Avenue, E-31, Cleveland, OH 44195, USA;2. Department of Neurosurgery, Center for Neuromodulation, Ohio State University Medical Center, Columbus, OH, USA;3. Department of Hospital Medicine and Outcomes Research, Cleveland Clinic, Cleveland, OH, USA;4. Department of General Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA;5. Postgraduate School, Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru;1. Affiliated Liuzhou Hospital of Southern Medical University, Liuzhou, Guangxi, China;2. The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China;3. Foshan Hospital of Traditional Chinese Medicine, Guangdong, China;4. The First People’s Hospital of Nanning, Nanning, China;5. Zhongshan Chenxinghai Hospital, Guangdong, China;6. Institute of Hospital Management, Chinese PLA General Hospital, Beijing, China;7. Continuing Learning College of Guangzhou University, Guangdong, China;1. Department of Neurology, Clinical Dementia Center, Georg August University Medical Center, Robert-Koch-Str. 40, 37075 Goettingen, Germany;2. Department of Clinical Chemistry, Georg August University Medical Center, Goettingen, Germany;3. Department of Statistics and Bioinformatics, Georg August University Medical Center, Goettingen, Germany;4. DZNE - German Center for Neurodegenerative Diseases, Germany;1. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantanxili, Dongcheng District, Beijing 100050, China;2. INI Stroke Center & Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria, IL, USA |
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| 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. |
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| Keywords: | Anaplastic oligoastrocytomas Chromosome region maintenance protein 1/exportin 1 IDH1-R132H mutation status Karyopherin a2/importin 1 |
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