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IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors

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Abstract

A total of 343 brain tumors were studied for IDH1 and IDH2 mutations by direct sequencing and for protein expression by immunohistochemistry with mIDH1R132H antibody. Of these, 287 were gliomas (17 pilocytic astrocytomas, 13 grade II and 5 grade III astrocytomas, 167 primary (pGBMs) and 19 secondary (sGBMs) glioblastomas, 36 grade II and 26 grade III oligodendrogliomas and 4 grade II–III oligoastrocytomas). In gliomas, IDH1 mutations at codon R132 were identified in 22.3%, of which 93.7% were c.395G>A (p.R132H). Mutations were more frequent in oligodendrogliomas (53.2%) than in astrocytic tumors (22.8%) and in sGBMs (84.2%) upon pGBMs (1.8%). There was a statistically significant correlation between mIDH1R132H antibody immunostaining and the relevant mutation c.395G>A (p.R132H) (P = 0.0001). No mutations were identified in non-glial tumors which were also negative to immunohistochemistry, with the exception of one PNET. A c.515G>T (p.R172M) mutation of the IDH2 gene was only identified in a grade II oligodendroglioma patient which was wild-type for IDH1. A direct correlation with MGMT promoter hypermethylation status and an inverse correlation with EGFR amplification was found, whereas the relationships with 1p/19q co-deletion and TP53 mutations only showed a trend toward correlation. In all gliomas, a positive correlation was found between IDH1 mutations and a young age (P = 0.0001). In contrast, a correlation with overall survival could only be obtained in low-grade gliomas. Immunohistochemistry appeared to be useful in differential diagnoses, especially toward non-tumor pathologic nervous tissue, and in recognizing infiltrating glioma cells. The mIDH1R132H antibody positivity was complementary with Cyclin D1 expression.

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Acknowledgements

This study was supported by a grant from Compagnia di San Paolo, Turin, Italy. We are greatly indebted to dr Bianca Pollo of Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Milan, Italy, for providing a quota of sGBMs. Angela Piazzi is a PhD student in Molecular Medicine at University of Piemonte Orientale.

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Authors and Affiliations

  1. Neuro-Bio-Oncology Center, Policlinico di Monza Foundation, University of Turin, Via Pietro Micca 29, 13100, Vercelli, Italy

    Marta Mellai, Valentina Caldera, Oriana Monzeglio & Davide Schiffer

  2. Department of Medical Sciences, University of Piemonte Orientale, Novara, Italy

    Angela Piazzi

  3. Department of Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy

    Paola Cassoni

  4. Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara, Italy

    Guido Valente

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  1. Marta Mellai
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  2. Angela Piazzi
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Correspondence to Davide Schiffer.

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Mellai, M., Piazzi, A., Caldera, V. et al. IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors. J Neurooncol 105, 345–357 (2011). https://doi.org/10.1007/s11060-011-0596-3

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  • DOI: https://doi.org/10.1007/s11060-011-0596-3

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