Skip to main content
Erschienen in: Journal of Neuro-Oncology 2/2014

01.06.2014 | Clinical Study

Karyopherin a2 and chromosome region maintenance protein 1 expression in meningiomas: novel biomarkers for recurrence and malignant progression

verfasst von: Konstantinos Gousias, Pitt Niehusmann, Gerrit H. Gielen, Matthias Simon

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat van Alkemade H, de Leau M, Dieleman EM et al (2012) Impaired survival and long-term neurological problems in benign meningioma. Neuro Oncol 14(5):658–666PubMedCentralPubMedCrossRef van Alkemade H, de Leau M, Dieleman EM et al (2012) Impaired survival and long-term neurological problems in benign meningioma. Neuro Oncol 14(5):658–666PubMedCentralPubMedCrossRef
4.
Zurück zum Zitat Rogers L, Gilbert M, Vogelbaum MA (2010) Intracranial meningiomas of atypical (WHO grade II) histology. J Neurooncol 99(3):393–405PubMedCrossRef Rogers L, Gilbert M, Vogelbaum MA (2010) Intracranial meningiomas of atypical (WHO grade II) histology. J Neurooncol 99(3):393–405PubMedCrossRef
5.
Zurück zum Zitat Abry E, Thomassen I, Salvesen O, Torp SH (2010) The significance of Ki-67/MIB-1 labeling index in human meningiomas: a literature study. Pathol Res Pract 206(12):810–815PubMedCrossRef Abry E, Thomassen I, Salvesen O, Torp SH (2010) The significance of Ki-67/MIB-1 labeling index in human meningiomas: a literature study. Pathol Res Pract 206(12):810–815PubMedCrossRef
6.
Zurück zum Zitat Oya S, Kawai K, Nakatomi H, Saito N (2012) Significance of Simpson grading system in modern meningioma surgery: integration of the grade with MIB-1 labeling index as a key to predict the recurrence of WHO Grade I meningiomas. J Neurosurg 117(1):121–128PubMedCrossRef Oya S, Kawai K, Nakatomi H, Saito N (2012) Significance of Simpson grading system in modern meningioma surgery: integration of the grade with MIB-1 labeling index as a key to predict the recurrence of WHO Grade I meningiomas. J Neurosurg 117(1):121–128PubMedCrossRef
7.
Zurück zum Zitat Zannini L, Lecis D, Lisanti S et al (2003) Karyophrin- a2 protein interacts with Chk2 and contributes to its nuclear import. J Biol Chem 278:42346–42351PubMedCrossRef Zannini L, Lecis D, Lisanti S et al (2003) Karyophrin- a2 protein interacts with Chk2 and contributes to its nuclear import. J Biol Chem 278:42346–42351PubMedCrossRef
8.
Zurück zum Zitat Tseng SF, Chang CY, Wu KJ, Teng SC (2005) Importin KPNA2 is required for proper nuclear localization and multiple functions of NSB1. J Biol Chem 280:39594–39600PubMedCrossRef Tseng SF, Chang CY, Wu KJ, Teng SC (2005) Importin KPNA2 is required for proper nuclear localization and multiple functions of NSB1. J Biol Chem 280:39594–39600PubMedCrossRef
9.
Zurück zum Zitat Chen YC, Su YN, Chou PC et al (2005) Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt. J Biol Chem 280(37):32505–32511PubMedCrossRef Chen YC, Su YN, Chou PC et al (2005) Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt. J Biol Chem 280(37):32505–32511PubMedCrossRef
10.
Zurück zum Zitat Kim IS, Kim DH, Han SM et al (2000) Truncated form of importin a identified in breast cancer cell inhibits nuclear import of p53. J Biol Chem 275:23139–23145PubMedCrossRef Kim IS, Kim DH, Han SM et al (2000) Truncated form of importin a identified in breast cancer cell inhibits nuclear import of p53. J Biol Chem 275:23139–23145PubMedCrossRef
11.
Zurück zum Zitat Noetzel E, Rose M, Bornemann J, Gajewski M, Knüchel R, Dahl E (2012) Nuclear transport receptor karyopherin-a2 promotes malignant breast cancer phenotypes in vitro. Oncogene 31(16):2101–2114PubMedCrossRef Noetzel E, Rose M, Bornemann J, Gajewski M, Knüchel R, Dahl E (2012) Nuclear transport receptor karyopherin-a2 promotes malignant breast cancer phenotypes in vitro. Oncogene 31(16):2101–2114PubMedCrossRef
12.
Zurück zum Zitat Yashiroda Y, Yoshida M (2003) Nucleo-cytoplasmic transport of proteins as a target for therapeutic drugs. Curr Med Chem 10(9):741–748PubMedCrossRef Yashiroda Y, Yoshida M (2003) Nucleo-cytoplasmic transport of proteins as a target for therapeutic drugs. Curr Med Chem 10(9):741–748PubMedCrossRef
13.
Zurück zum Zitat Turner JG, Dawson J, Sullivan DM (2012) Nuclear export of proteins and drug resistance in cancer. Biochem Pharmacol 83(8):1021–1032PubMedCrossRef Turner JG, Dawson J, Sullivan DM (2012) Nuclear export of proteins and drug resistance in cancer. Biochem Pharmacol 83(8):1021–1032PubMedCrossRef
14.
Zurück zum Zitat Fukuda M, Asano S, Nakamura T et al (1997) CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 390(6657):308–311PubMedCrossRef Fukuda M, Asano S, Nakamura T et al (1997) CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 390(6657):308–311PubMedCrossRef
15.
Zurück zum Zitat Inoue H, Kauffman M, Shacham S et al (2013) CRM1 blockade by selective inhibitors of nuclear export attenuates kidney cancer growth. J Urol 189(6):2317–2326PubMedCrossRef Inoue H, Kauffman M, Shacham S et al (2013) CRM1 blockade by selective inhibitors of nuclear export attenuates kidney cancer growth. J Urol 189(6):2317–2326PubMedCrossRef
16.
Zurück zum Zitat Etchin J, Sanda T, Mansour MR et al (2013) KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. Br J Haematol 161(1):117–127PubMedCentralPubMedCrossRef Etchin J, Sanda T, Mansour MR et al (2013) KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. Br J Haematol 161(1):117–127PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Zheng M, Tang L, Huang L et al (2010) Overexpression of karyopherin-2 in epithelial ovarian cancer and correlation with poor prognosis. Obstet Gynecol 116(4):884–891PubMedCrossRef Zheng M, Tang L, Huang L et al (2010) Overexpression of karyopherin-2 in epithelial ovarian cancer and correlation with poor prognosis. Obstet Gynecol 116(4):884–891PubMedCrossRef
18.
Zurück zum Zitat Dahl E, Kristiansen G, Gottlob K et al (2006) Molecular profiling of laser-microdissected matched tumor and normal breast tissue identifies karyopherin a2 as a potential novel prognostic marker in breast cancer. Clin Cancer Res 12(13):3950–3960PubMedCrossRef Dahl E, Kristiansen G, Gottlob K et al (2006) Molecular profiling of laser-microdissected matched tumor and normal breast tissue identifies karyopherin a2 as a potential novel prognostic marker in breast cancer. Clin Cancer Res 12(13):3950–3960PubMedCrossRef
19.
Zurück zum Zitat van der Watt PJ, Maske CP, Hendricks DT et al (2009) The karyopherin proteins, Crm1 and Karyopherin b1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int J Cancer 124:1829–1840PubMedCrossRef van der Watt PJ, Maske CP, Hendricks DT et al (2009) The karyopherin proteins, Crm1 and Karyopherin b1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int J Cancer 124:1829–1840PubMedCrossRef
20.
Zurück zum Zitat Mortezavi A, Hermanns T, Seifert HH et al (2011) KPNA2 expression is an independent adverse predictor of biochemical recurrence after radical prostatectomy. Clin Cancer Res 17(5):1111–1121PubMedCrossRef Mortezavi A, Hermanns T, Seifert HH et al (2011) KPNA2 expression is an independent adverse predictor of biochemical recurrence after radical prostatectomy. Clin Cancer Res 17(5):1111–1121PubMedCrossRef
21.
Zurück zum Zitat Winnepenninckx V, Lazar V, Michiels S et al (2006) Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst 98(7):472–482PubMedCrossRef Winnepenninckx V, Lazar V, Michiels S et al (2006) Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst 98(7):472–482PubMedCrossRef
22.
Zurück zum Zitat Yao Y, Dong Y, Lin F et al (2009) The expression of CRM1 is associated with prognosis in human osteosarcoma. Oncol Rep 21(1):229–235PubMed Yao Y, Dong Y, Lin F et al (2009) The expression of CRM1 is associated with prognosis in human osteosarcoma. Oncol Rep 21(1):229–235PubMed
23.
Zurück zum Zitat Forgues M, Difilippantonio MJ, Linke SP et al (2003) Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles. Mol Cell Biol 23(15):5282–5292PubMedCentralPubMedCrossRef Forgues M, Difilippantonio MJ, Linke SP et al (2003) Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles. Mol Cell Biol 23(15):5282–5292PubMedCentralPubMedCrossRef
24.
Zurück zum Zitat Gousias K, Becker AJ, Simon M, Niehusmann P (2012) Nuclear karyopherin a2: a novel biomarker for infiltrative astrocytomas. J Neurooncol 109(3):545–553PubMedCrossRef Gousias K, Becker AJ, Simon M, Niehusmann P (2012) Nuclear karyopherin a2: a novel biomarker for infiltrative astrocytomas. J Neurooncol 109(3):545–553PubMedCrossRef
25.
Zurück zum Zitat Shen A, Wang Y, Zhao Y, Zou L, Sun L, Cheng C (2009) Expression of CRM1 in human gliomas and its significance in p27 expression and clinical prognosis. Neurosurgery 65(1):153–160PubMedCrossRef Shen A, Wang Y, Zhao Y, Zou L, Sun L, Cheng C (2009) Expression of CRM1 in human gliomas and its significance in p27 expression and clinical prognosis. Neurosurgery 65(1):153–160PubMedCrossRef
26.
Zurück zum Zitat Nguyen KT, Holloway MP, Altura RA (2012) The CRM1 nuclear export protein in normal development and disease. Int J Biochem Mol Biol 3(2):137–151PubMedCentralPubMed Nguyen KT, Holloway MP, Altura RA (2012) The CRM1 nuclear export protein in normal development and disease. Int J Biochem Mol Biol 3(2):137–151PubMedCentralPubMed
27.
Zurück zum Zitat Teng SC, Wu KJ, Tseng SF, Wong CW, Kao L (2006) Importin KPNA2, NSB1, DNA repair and tumorigenesis. J Mol Histol 37:293–299PubMedCrossRef Teng SC, Wu KJ, Tseng SF, Wong CW, Kao L (2006) Importin KPNA2, NSB1, DNA repair and tumorigenesis. J Mol Histol 37:293–299PubMedCrossRef
28.
Zurück zum Zitat Sotiriou C, Wirapati P, Loi S et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histological grade to improve prognosis. J Natl Cancer Inst 98:262–272PubMedCrossRef Sotiriou C, Wirapati P, Loi S et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histological grade to improve prognosis. J Natl Cancer Inst 98:262–272PubMedCrossRef
29.
Zurück zum Zitat Wang CI, Wang CL, Wang CW et al (2010) Importin subunit alpha-2 is identified as a potential biomarker for non-small cell lung cancer by integration of the cancer cell secretome and tissue transcriptome. Int J Cancer 128(10):2364–2372CrossRef Wang CI, Wang CL, Wang CW et al (2010) Importin subunit alpha-2 is identified as a potential biomarker for non-small cell lung cancer by integration of the cancer cell secretome and tissue transcriptome. Int J Cancer 128(10):2364–2372CrossRef
30.
Zurück zum Zitat Huang WY, Yue L, Qiu WS, Wang LW, Zhou XH, Sun YJ (2009) Prognostic value of CRM1 in pancreas cancer. Clin Invest Med 32(6):E315PubMed Huang WY, Yue L, Qiu WS, Wang LW, Zhou XH, Sun YJ (2009) Prognostic value of CRM1 in pancreas cancer. Clin Invest Med 32(6):E315PubMed
31.
Zurück zum Zitat Noske A, Weichert W, Niesporek S et al (2008) Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer. Cancer 112(8):1733–1743PubMedCrossRef Noske A, Weichert W, Niesporek S et al (2008) Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer. Cancer 112(8):1733–1743PubMedCrossRef
32.
Zurück zum Zitat Mair R, Morris K, Scott I, Carroll TA (2011) Radiotherapy for atypical meningiomas. J Neurosurg 115(4):811–819PubMedCrossRef Mair R, Morris K, Scott I, Carroll TA (2011) Radiotherapy for atypical meningiomas. J Neurosurg 115(4):811–819PubMedCrossRef
33.
Zurück zum Zitat Gluz O, Wild P, Meiler R et al (2008) Nuclear karyopherin a2 expression predicts poor survival in patients with advanced breast cancer irrespective of treatment intensity. Int J Cancer 123:1433–1438PubMedCrossRef Gluz O, Wild P, Meiler R et al (2008) Nuclear karyopherin a2 expression predicts poor survival in patients with advanced breast cancer irrespective of treatment intensity. Int J Cancer 123:1433–1438PubMedCrossRef
Metadaten
Titel
Karyopherin a2 and chromosome region maintenance protein 1 expression in meningiomas: novel biomarkers for recurrence and malignant progression
verfasst von
Konstantinos Gousias
Pitt Niehusmann
Gerrit H. Gielen
Matthias Simon
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 2/2014
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-014-1423-4

Weitere Artikel der Ausgabe 2/2014

Journal of Neuro-Oncology 2/2014 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Demenzkranke durch Antipsychotika vielfach gefährdet

Demenz Nachrichten

Der Einsatz von Antipsychotika gegen psychische und Verhaltenssymptome in Zusammenhang mit Demenzerkrankungen erfordert eine sorgfältige Nutzen-Risiken-Abwägung. Neuen Erkenntnissen zufolge sind auf der Risikoseite weitere schwerwiegende Ereignisse zu berücksichtigen.

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.