December 20, 2011 — Diffuse glioma should be addressed not as a focal disease but rather as a systemic disease of the entire brain, conclude researchers from Germany and the Netherlands in a report published online December 12 in the Archives of Neurology.
In a study of brain tissue samples from 4 patients with diffuse glioma, the researchers report that they detected single tumor cells in areas of the brain that appeared "inconspicuous macroscopically and at histological analysis with respect to cellularity, cellular pleomorphism, and mitotic activity."
Long-standing Problem
Determining the extent of infiltration in diffuse glioma has been a long-standing diagnostic problem, Felix Sahm, MD, from the Department of Neuropathology, Institute of Pathology, German Cancer Research Center in Heidelberg, and colleagues note in their report.
Until now, all approaches have been limited by the fact that single neoplastic glial tumor cells often cannot be distinguished from normal or reactive cells on grounds of morphology or immunocytochemical profile.
It has been shown recently that mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) are present in most diffuse gliomas. The vast majority of the IDH1 mutations in glioma are characterized by exchange of an arginine by a histidine residue in position 132 of the protein (R132H).
Dr. Sahm and colleagues say a monoclonal antibody recognizing the R132H mutation called H09 has recently been generated. It detects single tumor cells and reliably distinguishes neoplastic cells from other cells.
In the current study, they applied this antibody to paraffin-embedded whole-brain and hemispheric sections from 4 patients with glioma known to harbor IDH1 R132H mutation.
"[W]e were able to unequivocally detect tumor cells where no certain discrimination between reactive and malignant cells could be drawn by means of histopathological analysis," they report.
"Detection of single tumor cells throughout the brain demonstrates diffuse glioma to represent systemic brain disease," Dr. Sahm and colleagues conclude.
Important Clinical Implications
"I like this report, it's very neat," Hai Yan, MD, PhD, from the Division of Pathology Research, Duke University School of Medicine, in Durham, North Carolina, who has studied IDH1 mutations in gliomas, told Medscape Medical News.
The authors, Dr. Yan said, "took advantage of a newly identified tumor marker IDH1 mutation and developed an IHC [immunohistochemical] method to detect single tumor cells containing IDH1 mutation in situ. It will have important clinical implication in brain tumor diagnosis," Dr. Yan predicted.
Dr. Sahm and colleagues suggest further studies are needed to determine whether mutated IDH1 protein allows specific targeting of all tumor cells.
They also note that the 4 patients studied had end-stage gliomas; therefore, status of infiltration at first presentation of disease cannot be determined. In addition, because all of the tumors harbored IDH1 R132H mutation, no conclusions can be drawn for IDH wild-type tumors, they say.
The research was supported by grants from Bundesministerium fur Bildung und Forschung. Two of the authors share royalties received by the German Cancer Research Center on the sales of H09 antibody. Dr. Yan has disclosed no relevant financial relationships.
Arch Neuro. 2011. Published online December 12, 2011. Abstract
In a study of brain tissue samples from 4 patients with diffuse glioma, the researchers report that they detected single tumor cells in areas of the brain that appeared "inconspicuous macroscopically and at histological analysis with respect to cellularity, cellular pleomorphism, and mitotic activity."
Long-standing Problem
Determining the extent of infiltration in diffuse glioma has been a long-standing diagnostic problem, Felix Sahm, MD, from the Department of Neuropathology, Institute of Pathology, German Cancer Research Center in Heidelberg, and colleagues note in their report.
Until now, all approaches have been limited by the fact that single neoplastic glial tumor cells often cannot be distinguished from normal or reactive cells on grounds of morphology or immunocytochemical profile.
It has been shown recently that mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) are present in most diffuse gliomas. The vast majority of the IDH1 mutations in glioma are characterized by exchange of an arginine by a histidine residue in position 132 of the protein (R132H).
Dr. Sahm and colleagues say a monoclonal antibody recognizing the R132H mutation called H09 has recently been generated. It detects single tumor cells and reliably distinguishes neoplastic cells from other cells.
In the current study, they applied this antibody to paraffin-embedded whole-brain and hemispheric sections from 4 patients with glioma known to harbor IDH1 R132H mutation.
"[W]e were able to unequivocally detect tumor cells where no certain discrimination between reactive and malignant cells could be drawn by means of histopathological analysis," they report.
"Detection of single tumor cells throughout the brain demonstrates diffuse glioma to represent systemic brain disease," Dr. Sahm and colleagues conclude.
Important Clinical Implications
"I like this report, it's very neat," Hai Yan, MD, PhD, from the Division of Pathology Research, Duke University School of Medicine, in Durham, North Carolina, who has studied IDH1 mutations in gliomas, told Medscape Medical News.
The authors, Dr. Yan said, "took advantage of a newly identified tumor marker IDH1 mutation and developed an IHC [immunohistochemical] method to detect single tumor cells containing IDH1 mutation in situ. It will have important clinical implication in brain tumor diagnosis," Dr. Yan predicted.
Dr. Sahm and colleagues suggest further studies are needed to determine whether mutated IDH1 protein allows specific targeting of all tumor cells.
They also note that the 4 patients studied had end-stage gliomas; therefore, status of infiltration at first presentation of disease cannot be determined. In addition, because all of the tumors harbored IDH1 R132H mutation, no conclusions can be drawn for IDH wild-type tumors, they say.
The research was supported by grants from Bundesministerium fur Bildung und Forschung. Two of the authors share royalties received by the German Cancer Research Center on the sales of H09 antibody. Dr. Yan has disclosed no relevant financial relationships.
Arch Neuro. 2011. Published online December 12, 2011. Abstract
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Hi there! glad to drop by your page and found these very interesting and informative stuff. Thanks for sharing, keep it up!
- glioma
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