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Alpha-internexin and altered CIC expression as a supportive diagnostic marker for oligodendroglial tumors with the 1p/19q co-deletion

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Abstract

α-Internexin (INA) has been proposed as a biomarker of oligodendroglial tumors with the 1p/19q co-deletion. On the other hand, sequence studies have recently linked the CIC mutation and subsequent altered CIC expression to the 1p/19q co-deletion in oligodendroglial tumors. We assessed the usability of combination immunohistochemical analysis using CIC and INA as a surrogate tool for the 1p/19q status in 39 cases of oligodendroglial tumors. The positive expression of INA was observed in 10 cases (52 %) of oligodendroglial tumors with the 1p/19q co-deletion, and in only 3 cases of oligodendroglial tumors without the 1p/19q co-deletion (15 %, P = 0.012). The lack of CIC expression was detected in 13 cases (68 %) of oligodendroglial tumors with the 1p/19q co-deletion, and in only 1 case of oligodendroglial tumors without the 1p/19q co-deletion (5 %, P < 0.0001). Combined immunohistochemical analysis assessed by INA expression and/or the lack of CIC expression was strongly associated with the 1p/19q co-deletion in oligodendroglial tumors, indicating a potential surrogate marker of the 1p/19q state. Although combined immunohistochemical analysis cannot be totally replaced by molecular genetic analysis as a definitive diagnostic technique, it may contribute to a steady morphological diagnosis by predicting the 1p/19q state in oligodendroglial tumors.

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References

  1. Bromberg JE, van den Bent MJ (2009) Oligodendrogliomas: molecular biology and treatment. Oncologist. United States 14:155–163

  2. Japan CoBTRo (2003) Report of Brain Tumor Registry of Japan (1969–1996). Neurol Med Chir (Tokyo) 43(Suppl i–vii):1–111

  3. Coons SW, Johnson PC, Scheithauer BW, Yates AJ, Pearl DK (1997) Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer 79:1381–1393

    Article  PubMed  CAS  Google Scholar 

  4. Giannini C, Burger PC, Berkey BA, Cairncross JG, Jenkins RB, Mehta M, Curran WJ, Aldape K (2008) Anaplastic oligodendroglial tumors: refining the correlation among histopathology, 1p 19q deletion and clinical outcome in Intergroup Radiation Therapy Oncology Group Trial 9402. Brain Pathol 18:360–369

    Article  PubMed  Google Scholar 

  5. Weller M, Berger H, Hartmann C, Schramm J, Westphal M, Simon M, Goldbrunner R, Krex D, Steinbach JP, Ostertag CB, Loeffler M, Pietsch T, von Deimling A (2007) Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker? Clin Cancer Res 13:6933–6937

    Article  PubMed  CAS  Google Scholar 

  6. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO Classification of Tumours of the Central Nervous System. IARC, Lyon

    Google Scholar 

  7. Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP (1994) Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 145:1175–1190

    PubMed  CAS  PubMed Central  Google Scholar 

  8. Bello MJ, Leone PE, Vaquero J, de Campos JM, Kusak ME, Sarasa JL, Pestana A, Rey JA (1995) Allelic loss at 1p and 19q frequently occurs in association and may represent early oncogenic events in oligodendroglial tumors. Int J Cancer 64:207–210

    Article  PubMed  CAS  Google Scholar 

  9. Kraus JA, Koopmann J, Kaskel P, Maintz D, Brandner S, Schramm J, Louis DN, Wiestler OD, von Deimling A (1995) Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma. J Neuropathol Exp Neurol 54:91–95

    Article  PubMed  CAS  Google Scholar 

  10. Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479

    Article  PubMed  CAS  Google Scholar 

  11. McDonald JM, See SJ, Tremont IW, Colman H, Gilbert MR, Groves M, Burger PC, Louis DN, Giannini C, Fuller G, Passe S, Blair H, Jenkins RB, Yang H, Ledoux A, Aaron J, Tipnis U, Zhang W, Hess K, Aldape K (2005) The prognostic impact of histology and 1p/19q status in anaplastic oligodendroglial tumors. Cancer 104:1468–1477

    Article  PubMed  CAS  Google Scholar 

  12. Sasaki H, Zlatescu MC, Betensky RA, Johnk LB, Cutone AN, Cairncross JG, Louis DN (2002) Histopathological-molecular genetic correlations in referral pathologist-diagnosed low-grade “oligodendroglioma”. J Neuropathol Exp Neurol 61:58–63

    PubMed  Google Scholar 

  13. Smith JS, Perry A, Borell TJ, Lee HK, O’Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18:636–645

    PubMed  CAS  Google Scholar 

  14. van den Bent MJ, Looijenga LH, Langenberg K, Dinjens W, Graveland W, Uytdewilligen L, Sillevis Smitt PA, Jenkins RB, Kros JM (2003) Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features. Cancer 97:1276–1284

    Article  PubMed  Google Scholar 

  15. van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T (2006) Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 24:2715–2722

    Article  PubMed  Google Scholar 

  16. Mokhtari K, Ducray F, Kros JM, Gorlia T, Idbaih A, Taphoorn M, Wesseling P, Hoang-Xuan K, Van den Bent M, Sanson M (2011) Alpha-internexin expression predicts outcome in anaplastic oligodendroglial tumors and may positively impact the efficacy of chemotherapy: European organization for research and treatment of cancer trial 26951. Cancer 117:3014–3026

    Article  PubMed  CAS  Google Scholar 

  17. Buckley PG, Alcock L, Heffernan J, Woods J, Brett F, Stallings RL, Farrell MA (2011) Loss of chromosome 1p/19q in oligodendroglial tumors: refinement of chromosomal critical regions and evaluation of internexin immunostaining as a surrogate marker. J Neuropathol Exp Neurol 70:177–182

    Article  PubMed  Google Scholar 

  18. Ducray F, Criniere E, Idbaih A, Mokhtari K, Marie Y, Paris S, Navarro S, Laigle-Donadey F, Dehais C, Thillet J, Hoang-Xuan K, Delattre JY, Sanson M (2009) Alpha-internexin expression identifies 1p19q codeleted gliomas. Neurology 72:156–161

    Article  PubMed  CAS  Google Scholar 

  19. Lariviere RC, Julien JP (2004) Functions of intermediate filaments in neuronal development and disease. J Neurobiol 58:131–148

    Article  PubMed  CAS  Google Scholar 

  20. Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH, Rodriguez FJ, Cahill DP, McLendon R, Riggins G, Velculescu VE, Oba-Shinjo SM, Marie SK, Vogelstein B, Bigner D, Yan H, Papadopoulos N, Kinzler KW (2011) Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 333:1453–1455

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Sahm F, Koelsche C, Meyer J, Pusch S, Lindenberg K, Mueller W, Herold-Mende C, von Deimling A, Hartmann C (2012) CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas. Acta Neuropathol 123:853–860

    Article  PubMed  CAS  Google Scholar 

  22. Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J, Birol I, Chesnelong C, Chiu R, Chuah E, Corbett R, Docking R, Firme M, Hirst M, Jackman S, Karsan A, Li H, Louis DN, Maslova A, Moore R, Moradian A, Mungall KL, Perizzolo M, Qian J, Roldan G, Smith EE, Tamura-Wells J, Thiessen N, Varhol R, Weiss S, Wu W, Young S, Zhao Y, Mungall AJ, Jones SJ, Morin GB, Chan JA, Cairncross JG, Marra MA (2012) Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. J Pathol 226:7–16

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Nigro JM, Takahashi MA, Ginzinger DG, Law M, Passe S, Jenkins RB, Aldape K (2001) Detection of 1p and 19q loss in oligodendroglioma by quantitative microsatellite analysis, a real-time quantitative polymerase chain reaction assay. Am J Pathol 158:1253–1262

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Biernat W, Huang H, Yokoo H, Kleihues P, Ohgaki H (2004) Predominant expression of mutant EGFR (EGFRvIII) is rare in primary glioblastomas. Brain Pathol 14:131–136

    Article  PubMed  CAS  Google Scholar 

  25. Chien CL, Liu TC, Ho CL, Lu KS (2005) Overexpression of neuronal intermediate filament protein alpha-internexin in PC12 cells. J Neurosci Res 80:693–706

    Article  PubMed  CAS  Google Scholar 

  26. Kaplan MP, Chin SS, Fliegner KH, Liem RK (1990) Alpha-internexin, a novel neuronal intermediate filament protein, precedes the low molecular weight neurofilament protein (NF-L) in the developing rat brain. J Neurosci 10:2735–2748

    PubMed  CAS  Google Scholar 

  27. Fliegner KH, Kaplan MP, Wood TL, Pintar JE, Liem RK (1994) Expression of the gene for the neuronal intermediate filament protein alpha-internexin coincides with the onset of neuronal differentiation in the developing rat nervous system. J Comp Neurol 342:161–173

    Article  PubMed  CAS  Google Scholar 

  28. Foley J, Witte D, Chiu FC, Parysek LM (1994) Expression of the neural intermediate filament proteins peripherin and neurofilament-66/alpha-internexin in neuroblastoma. Lab Invest 71:193–199

    PubMed  CAS  Google Scholar 

  29. Kaya B, Mena H, Miettinen M, Rushing EJ (2003) Alpha-internexin expression in medulloblastomas and atypical teratoid-rhabdoid tumors. Clin Neuropathol 22:215–221

    PubMed  CAS  Google Scholar 

  30. Ducray F, Idbaih A, de Reynies A, Bieche I, Thillet J, Mokhtari K, Lair S, Marie Y, Paris S, Vidaud M, Hoang-Xuan K, Delattre O, Delattre JY, Sanson M (2008) Anaplastic oligodendrogliomas with 1p19q co-deletion have a proneural gene expression profile. Mol Cancer 7:41

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ferrer-Luna R, Mata M, Nunez L, Calvar J, Dasi F, Arias E, Piquer J, Cerda-Nicolas M, Taratuto AL, Sevlever G, Celda B, Martinetto H (2009) Loss of heterozygosity at 1p-19q induces a global change in oligodendroglial tumor gene expression. J Neurooncol 95:343–354

    Article  PubMed  CAS  Google Scholar 

  32. Tanaka Y, Nobusawa S, Yagi S, Ikota H, Yokoo H, Nakazato Y (2012) Anaplastic oligodendroglioma with ganglioglioma-like maturation. Brain Tumor Pathol 29:221–228

    Article  PubMed  Google Scholar 

  33. Patt S, Labrakakis C, Bernstein M, Weydt P, Cervos-Navarro J, Nisch G, Kettenmann H (1996) Neuron-like physiological properties of cells from human oligodendroglial tumors. Neuroscience 71:601–611

    Article  PubMed  CAS  Google Scholar 

  34. Tseng AS, Tapon N, Kanda H, Cigizoglu S, Edelmann L, Pellock B, White K, Hariharan IK (2007) Capicua regulates cell proliferation downstream of the receptor tyrosine kinase/ras signaling pathway. Curr Biol 17:728–733

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Jimenez G, Guichet A, Ephrussi A, Casanova J (2000) Relief of gene repression by torso RTK signaling: role of capicua in Drosophila terminal and dorsoventral patterning. Genes Dev 14:224–231

    PubMed  CAS  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported in part by a grant from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (No. 21500335). The funders had no role in the study design, data collection and analysis, publication decision, or manuscript preparation.

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Authors and Affiliations

  1. Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Masaya Nagaishi, Aya Suzuki, Sumihito Nobusawa, Hideaki Yokoo & Yoichi Nakazato

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  1. Masaya Nagaishi
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  2. Aya Suzuki
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  3. Sumihito Nobusawa
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Correspondence to Masaya Nagaishi.

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Nagaishi, M., Suzuki, A., Nobusawa, S. et al. Alpha-internexin and altered CIC expression as a supportive diagnostic marker for oligodendroglial tumors with the 1p/19q co-deletion. Brain Tumor Pathol 31, 257–264 (2014). https://doi.org/10.1007/s10014-013-0168-7

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