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

• Published in: Journal of neuro-oncology Vol. 105; no. 2; pp. 345 - 357
• Main Authors: Mellai, Marta, Piazzi, Angela, Caldera, Valentina, Monzeglio, Oriana, Cassoni, Paola, Valente, Guido, Schiffer, Davide
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.11.2011; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - mortality; Clinical Study – Patient Study; DNA Methylation; DNA Modification Methylases - genetics; DNA Repair Enzymes - genetics; DNA, Neoplasm - genetics; Female; Glioma - genetics; Glioma - metabolism; Glioma - mortality; Humans; Immunoenzyme Techniques; Isocitrate Dehydrogenase - genetics; Medicine; Medicine & Public Health; Middle Aged; Mutation - genetics; Neurology; Oncology; Polymerase Chain Reaction; Prognosis; Promoter Regions, Genetic - genetics; Receptor, Epidermal Growth Factor - genetics; Survival Rate; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Proteins - genetics; Young Adult; Immunohistochemistry; mutations; and; Brain tumors
• DOI: 10.1007/s11060-011-0596-3
• ISSN: 0167-594X

A total of 343 brain tumors were studied for IDH1 and IDH2 mutations by direct sequencing and for protein expression by immunohistochemistry with mIDH1 R132H 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 mIDH1 R132H 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 mIDH1 R132H antibody positivity was complementary with Cyclin D1 expression.