Addressing diffuse glioma as a systemic brain disease with single-cell analysis.

OBJECTIVE To analyze infiltration patterns of IDH1 mutant diffuse gliomas into the brain by identification of single tumor cells applying an antibody specific to mutant IDH1 R132H protein. DESIGN Immunohistochemical analysis. SETTING University hospital. PATIENTS Whole-brain and hemisphere sections of 4 patients diagnosed with diffuse glioma. RESULTS Tumor cells were identified in areas that appeared inconspicuous macroscopically and at histological analysis with respect to cellularity, cellular pleomorphism, or mitotic activity in all cases. CONCLUSION Detection of single tumor cells throughout the brain demonstrates diffuse glioma to represent systemic brain disease.

[1]  H. Zentgraf,et al.  Monoclonal antibody specific for IDH1 R132H mutation , 2009, Acta Neuropathologica.

[2]  Christian Mawrin,et al.  Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas , 2009, Acta Neuropathologica.

[3]  M. Essig,et al.  Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes , 2010, Acta Neuropathologica.

[4]  A. von Deimling,et al.  Application of Mutant IDH1 Antibody to Differentiate Diffuse Glioma From Nonneoplastic Central Nervous System Lesions and Therapy-induced Changes , 2010, The American journal of surgical pathology.

[5]  R. Virchow.  Die krankhaften Geschwülste : dreissig Vorlesungen, gehalten während des Wintersemesters 1862-1863 an der Universität zu Berlin , 1863 .

[6]  H. Zentgraf,et al.  Characterization of R132H Mutation‐specific IDH1 Antibody Binding in Brain Tumors , 2010, Brain pathology.

[7]  D. Louis,et al.  Mutant IDH1-specific immunohistochemistry distinguishes diffuse astrocytoma from astrocytosis , 2009, Acta Neuropathologica.

[8]  B. Scheithauer,et al.  The 2007 WHO classification of tumours of the central nervous system , 2007, Acta Neuropathologica.

[9]  H. Scherer,et al.  THE FORMS OF GROWTH IN GLIOMAS AND THEIR PRACTICAL SIGNIFICANCE , 1940 .

[10]  D. Louis.  WHO classification of tumours of the central nervous system , 2007 .

[11]  J. Uhm.  An Integrated Genomic Analysis of Human Glioblastoma Multiforme , 2009 .

[12]  P. Bailey,et al.  A classification of the tumors of the glioma group on a histogenetic basis with a correlated study of prognosis , 1970 .

[13]  R. McLendon,et al.  IDH1 and IDH2 mutations in gliomas. , 2009, The New England journal of medicine.

[14]  J. Hainfellner,et al.  Value and Limitations of Immunohistochemistry and Gene Sequencing for Detection of the IDH1-R132H Mutation in Diffuse Glioma Biopsy Specimens , 2011, Journal of neuropathology and experimental neurology.

[15]  P. Cassoni,et al.  IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors , 2011, Journal of Neuro-Oncology.

[16]  M. Berens,et al.  Autocrine factors that sustain glioma invasion and paracrine biology in the brain microenvironment. , 2007, Journal of the National Cancer Institute.

[17]  M. Westphal,et al.  Cost of migration: invasion of malignant gliomas and implications for treatment. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  Andrey Korshunov,et al.  Analysis of the IDH1 codon 132 mutation in brain tumors , 2008, Acta Neuropathologica.

[19]  D. Silbergeld,et al.  Isolation and characterization of human malignant glioma cells from histologically normal brain. , 1997, Journal of neurosurgery.