Skip to main content
Log in

Characterizing invading glioma cells based on IDH1-R132H and Ki-67 immunofluorescence

  • Original Article
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

Glioma, the most common primary brain tumor, is characterized by proliferative-invasive growth. However, the detailed biological characteristics of invading glioma cells remain to be elucidated. A monoclonal antibody (clone HMab-1) that specifically and sensitively recognizes the isocitrate dehydrogenase-1 (IDH1) protein carrying the R132H mutation can identify invading glioma cells by immunostaining. To investigate the degree of invasion in gliomas of distinct grades and the proliferative capacity of the invading cells, immunofluorescent staining was conducted using antibodies against IDH1-R132H and Ki-67 on 11 surgical and autopsy specimens of the tumor core and the invading area. Higher numbers of IDH1-R132H-positive cells in the invading area correlated with a higher tumor grade. Double staining for IDH1-R132H and Ki-67 demonstrated that most invading cells that expressed IDH1-R132H were not stained by the Ki-67 antibody, and the ratio of Ki-67-positive cells among IDH1-R132H-positive cells was significantly lower in the invasion area than in the tumor core in all grades of glioma. These data suggest that higher grade gliomas have a greater invasive potential and that invading cells possess low proliferative capacity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

IDH1:

Isocitrate dehydrogenase1

GBM:

Glioblastoma

References

  1. Nakada M, Nakada S, Demuth T et al (2007) Molecular targets of glioma invasion. Cell Mol Life Sci 64:458–478

    Article  PubMed  CAS  Google Scholar 

  2. Raghunathan A, Olar A, Vogel H et al (2012) Isocitrate dehydrogenase 1 R132H mutation is not detected in angio-centric glioma. Ann Diagn Pathol 16:255–259

    Article  PubMed  Google Scholar 

  3. Sayson M, Marie Y, Paris S et al (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154

    Article  Google Scholar 

  4. Capper D, Zentgraf H, Balss J et al (2009) Monoclonal antibody specific for IDH1 R132 mutation. Acta Neuropahtol 118:599–601

    Article  CAS  Google Scholar 

  5. Kaneko MK, Ogasawara S, Kato Y (2013) Establishment of a novel multi-specific monoclonal antibody MsMab-1 recognizing both IDH1 and IDH2 mutations. Tohoku J Exp Med 230:103–109

    Article  CAS  Google Scholar 

  6. Camelo-Piragua S, Jansen M, Ganguly A et al (2010) Mutant IDH-1 specific immunohistochemistry distinguishes diffuse astrocytoma from astrocytosis. Acta Neuropathol 119:509–511

    Article  PubMed  PubMed Central  Google Scholar 

  7. Giese A, Loo MA, Tran N et al (1996) Dichotomy of astrocytoma migration and proliferation. Int J Cancer 67:275–282

    Article  PubMed  CAS  Google Scholar 

  8. Mariani L, Beaudry C, McDonough WS et al (2001) Glioma cell motility is associated with reduced transcription of pro-apoptotic and proliferation genes: a cDNA microarray analysis. J Neurooncol 53:161–176

    Article  PubMed  CAS  Google Scholar 

  9. Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classification of tumors of the nervous system. Acta Neuropathol 114:97–109

    Article  PubMed  PubMed Central  Google Scholar 

  10. Nakada M, Kita D, Teng L et al (2013) Receptor tyrosine kinases: principles and functions in glioma invasion. Adv Exp Med Biol 986:143–170

    Article  PubMed  CAS  Google Scholar 

  11. Yoshida Y, Nakada M, Harada T et al (2010) The expression level of sphingosine-1 phosphate receptor type 1 is related to MIB-1 labeling index and predicts survival of glioblastoma patients. J Neurooncol 98:41–47

    Article  PubMed  CAS  Google Scholar 

  12. Oka H, Utsuki S, Tanizaki Y et al (2013) Clinicopathological features of human brainstem gliomas. Brain Tumor Pathol 30:1–7

    Article  PubMed  Google Scholar 

  13. Wang M, Wang T, Liu S et al (2003) The expression of matrix metalloproteinase-2 and-9 in human gliomas of different pathological grades. Brain Tumor Pathol 20:65–72

    Article  PubMed  Google Scholar 

  14. Nakada M, Nakamura H, Ikeda E et al (1999) Expression and tissue localization of membrane type-1, 2, and 3 matrix metalloproteinase in human astrocytic tumors. Am J Pathol 154:417–428

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Nakada M, Kita D, Futami K et al (2001) Roles of membrane type 1 matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases 2 in invasion and dissemination of human malignant glioma. J Neurosurg 94:464–473

    Article  PubMed  CAS  Google Scholar 

  16. Deng Z, Yan Y, Zhong D et al (2010) Quantitative analysis of glioma cell invasion by diffusion tensor imaging. J Clin Neurosci 17:1530–1536

    Article  PubMed  Google Scholar 

  17. Takano S, Tian W, Matsuda M et al (2011) Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing. Brain Tumor Pathol 28:115–123

    Article  PubMed  CAS  Google Scholar 

  18. Kloosterhof NK, Bralten LB, Dubbink HJ et al (2011) Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma? Lancet Oncol 12:83–91

    Article  PubMed  CAS  Google Scholar 

  19. Watanabe T, Nobusawa S, Kleihues P et al (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Giese A, Bjerkvig R, Berens ME et al (2003) Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol 21:1624–1636

    Article  PubMed  CAS  Google Scholar 

  21. Dalrymple SJ, Parisi JE, Roche PC et al (1994) Changes in proliferating cell nuclear antigen expression in glioblastoma multi-forme cells along a stereotactic biopsy trajectory. Neurosurgery 35:1036–1044

    Article  PubMed  CAS  Google Scholar 

  22. Schiffer D, Cavalla P, Dutto A et al (1997) Cell proliferation and invasion in malignant gliomas. Anticancer Res 17:61–69

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Akiko Imamura for help with immunohistochemistry.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mitsutoshi Nakada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sabit, H., Nakada, M., Furuta, T. et al. Characterizing invading glioma cells based on IDH1-R132H and Ki-67 immunofluorescence. Brain Tumor Pathol 31, 242–246 (2014). https://doi.org/10.1007/s10014-013-0172-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-013-0172-y

Keywords

Navigation