Prognostic stratification of gliomatosis cerebri by IDH1 R132H and INA expression.

Abstract

Gliomatosis cerebri (GC) constitutes a heterogeneous group of conditions involving diffuse neoplastic glial cell infiltration of the brain. Management is difficult and an obvious challenge is to identify prognostic factors. Alpha-internexin (INA) expression, which is closely related to the 1p19q codeletion, is a strong prognostic marker in oligodendroglial tumors. Similarly, the R132H isocitrate dehydrogenase 1 IDH1 mutation, which can now be detected by use of a specific antibody, predicts better outcome in gliomas. In a retrospective series of 40 GC treated with up-front chemotherapy, we analyzed IDH1(R132H) mutant protein and INA immunohistochemical expression and correlated it with outcome; 17/40 GC expressed IDH1(R132H) and 10/40 GC expressed INA. IDH1(R132H) staining was strongly related to progression-free survival (42.3 vs. 15.5 months for positive IDH1(R132H) vs. negative tumors; P < 0.0001) and overall survival (73.9 vs. 23.6 months; P < 0.0001). This effect was independent of grade, histologic subtype, and INA expression (P < 0.001). Combined expression of IDH1(R132H) and INA was strongly associated with response to chemotherapy (100% vs. 36%; P = 0.003). These data strongly suggest that INA and IDH1(R132H) mutant protein immunohistochemical analysis is of a great prognostic value in biopsied GC.

• Authors: Virginie Desestret, Pietro Ciccarino, François Ducray, Emmanuelle Crinière, Blandine Boisselier, Marianne Labussière, Marc Polivka, Ahmed Idbaih, Gentian Kaloshi, Andreas von Deimling, Khe Hoang-Xuan, Jean-Yves Delattre, Karima Mokhtari, Marc Sanson
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 105 Issue 2 Pg. 219-24 (Nov 2011) ISSN: 1573-7373 [Electronic] United States
• PMID: 21516462 (Publication Type: Journal Article)

Chemical References

• Intermediate Filament Proteins
• Mutant Proteins
• alpha-internexin
• Isocitrate Dehydrogenase
• IDH1 protein, human

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Follow-Up Studies
• Humans
• Immunoenzyme Techniques
• Intermediate Filament Proteins (metabolism)
• Isocitrate Dehydrogenase (metabolism)
• Mutant Proteins (metabolism)
• Neoplasms, Neuroepithelial (drug therapy, metabolism, mortality)
• Polymorphism, Single Nucleotide (genetics)
• Prognosis
• Retrospective Studies
• Survival Rate