Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing
Isocitrate dehydrogenase 1 (IDH1) mutations have recently been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas, as well as secondary glioblastomas, whereas primary glioblastomas very rarely contain IDH1 mutations. Furthermore, a specific monoclonal antibody, IMab-1, which recognizes IDH1-R132H—the most frequent IDH1 mutation—has been generated. IMab-1 has been reported to react with the IDH1-R132H protein, but not the wild-type IDH1 or the other IDH1 mutant proteins in Western-blot analysis. However, the importance of immunohistochemistry using IMab-1 has not yet been elucidated. In this study, we compared the findings from IMab-1 immunohistochemistry and direct DNA sequencing using 49 glioma samples. IMab-1 detected 12 out of 49 cases; however, only nine cases were found to be IDH1-R132H by direct DNA sequencing because of a small population of IDH1-R132H mutation-possessing tumor cells, indicating that IMab-1 immunohistochemistry is useful for detecting IDH1-R132H. We conducted immunohistochemical detection in 52 cases of grade III astrocytomas. The median time to progression (TTP) was significantly longer in the cases with the IDH1 mutation (86.7 months) compared to the cases without the IDH1 mutation (wild type, 10.4 months) (p < 0.01). In conclusion, the anti-IDH1-R132H-specific monoclonal antibody IMab-1 is very useful for detecting IDH1-R132H in immunohistochemistry, and predicting the time to progression in grade III anaplastic astrocytomas. Therefore, IMab-1 is likely to be useful for the diagnosis of mutation-bearing gliomas and for determining the treatment strategy of grade III gliomas.
KeywordsIDH1 Mutation Immunohistochemistry Monoclonal antibody Glioma
We gratefully acknowledge Yoshiko Tsukada and Makiko Miyakawa for their excellent technical assistance, and Chifumi Kitanaka for his great suggestion. IMab-1 antibody was kindly donated by Dr. Darell D. Bigner, Duke University Medical Center. This study was supported by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (S. T.), and by grants provided by the Tsukuba Advanced Research Alliance, the Japan Brain Foundation, the Japanese Foundation for Research and Promotion of Endoscopy, the Japanese Foundation for Multidisciplinary Treatment of Cancer (S.T.), the Global COE Program for Medical Sciences, the Japan Society for the Promotion of Science (Y. K. and M. K. K), and the Experimental and Research Center, North China Coal Medical University (W. T.).
- 11.van den Bent MJ, Dubbink HJ, Marie Y et al (2010) IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res 16:1597–1604Google Scholar
- 14.Mashiko R, Takano S, Ishikawa E et al (2010) Hypoxia-inducible factor 1α expression is a prognostic biomarker in patients with astrocytic tumors associated with necrosis on MR image. J Neuro Oncol (Epub ahead of print)Google Scholar