Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis

Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.

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References

Capper D, Weissert S, Balss J, Habel A, Meyer J, Jager D . Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol. 2009; 20(1):245-54. PMC: 8094636. DOI: 10.1111/j.1750-3639.2009.00352.x. View

Hegi M, Janzer R, Lambiv W, Gorlia T, Kouwenhoven M, Hartmann C . Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial. Acta Neuropathol. 2012; 123(6):841-52. DOI: 10.1007/s00401-011-0938-4. View

Giannini C, Burger P, Berkey B, Cairncross J, Jenkins R, Mehta M . Anaplastic oligodendroglial tumors: refining the correlation among histopathology, 1p 19q deletion and clinical outcome in Intergroup Radiation Therapy Oncology Group Trial 9402. Brain Pathol. 2008; 18(3):360-9. PMC: 8095535. DOI: 10.1111/j.1750-3639.2008.00129.x. View

Dehais C, Laigle-Donadey F, Marie Y, Kujas M, Lejeune J, Benouaich-Amiel A . Prognostic stratification of patients with anaplastic gliomas according to genetic profile. Cancer. 2006; 107(8):1891-7. DOI: 10.1002/cncr.22211. View

Verhaak R, Hoadley K, Purdom E, Wang V, Qi Y, Wilkerson M . Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010; 17(1):98-110. PMC: 2818769. DOI: 10.1016/j.ccr.2009.12.020. View

Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J . Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2012; 31(3):337-43. PMC: 3732012. DOI: 10.1200/JCO.2012.43.2674. View

Figarella-Branger D, Mokhtari K, Dehais C, Jouvet A, Uro-Coste E, Colin C . Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations. Neuro Oncol. 2014; 16(9):1244-54. PMC: 4136899. DOI: 10.1093/neuonc/nou047. View

Wang Y, Li S, Chen L, You G, Bao Z, Yan W . Glioblastoma with an oligodendroglioma component: distinct clinical behavior, genetic alterations, and outcome. Neuro Oncol. 2012; 14(4):518-25. PMC: 3309852. DOI: 10.1093/neuonc/nor232. View

Idbaih A, Ducray F, Dehais C, Courdy C, Carpentier C, de Bernard S . SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas. PLoS One. 2012; 7(10):e45950. PMC: 3468603. DOI: 10.1371/journal.pone.0045950. View

10.

Labussiere M, Idbaih A, Wang X, Marie Y, Boisselier B, Falet C . All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Neurology. 2010; 74(23):1886-90. DOI: 10.1212/WNL.0b013e3181e1cf3a. View

11.

Kraus J, Lamszus K, Glesmann N, Beck M, Wolter M, Sabel M . Molecular genetic alterations in glioblastomas with oligodendroglial component. Acta Neuropathol. 2001; 101(4):311-20. DOI: 10.1007/s004010000258. View

12.

Appin C, Gao J, Chisolm C, Torian M, Alexis D, Vincentelli C . Glioblastoma with oligodendroglioma component (GBM-O): molecular genetic and clinical characteristics. Brain Pathol. 2013; 23(4):454-61. PMC: 4868066. DOI: 10.1111/bpa.12018. View

13.

Miller C, Dunham C, Scheithauer B, Perry A . Significance of necrosis in grading of oligodendroglial neoplasms: a clinicopathologic and genetic study of newly diagnosed high-grade gliomas. J Clin Oncol. 2006; 24(34):5419-26. DOI: 10.1200/JCO.2006.08.1497. View

14.

van den Bent M, Carpentier A, Brandes A, Sanson M, Taphoorn M, Bernsen H . Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of.... J Clin Oncol. 2006; 24(18):2715-22. DOI: 10.1200/JCO.2005.04.6078. View

15.

Stupp R, Mason W, van den Bent M, Weller M, Fisher B, Taphoorn M . Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10):987-96. DOI: 10.1056/NEJMoa043330. View

16.

Louis D, Perry A, Burger P, Ellison D, Reifenberger G, von Deimling A . International Society Of Neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol. 2014; 24(5):429-35. PMC: 8029490. DOI: 10.1111/bpa.12171. View

17.

He J, Mokhtari K, Sanson M, Marie Y, Kujas M, Huguet S . Glioblastomas with an oligodendroglial component: a pathological and molecular study. J Neuropathol Exp Neurol. 2001; 60(9):863-71. DOI: 10.1093/jnen/60.9.863. View

18.

Houillier C, Wang X, Kaloshi G, Mokhtari K, Guillevin R, Laffaire J . IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology. 2010; 75(17):1560-6. DOI: 10.1212/WNL.0b013e3181f96282. View

19.

Joseph N, Phillips J, Dahiya S, Felicella M, Tihan T, Brat D . Diagnostic implications of IDH1-R132H and OLIG2 expression patterns in rare and challenging glioblastoma variants. Mod Pathol. 2012; 26(3):315-26. DOI: 10.1038/modpathol.2012.173. View

20.

Sahm F, Reuss D, Koelsche C, Capper D, Schittenhelm J, Heim S . Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma. Acta Neuropathol. 2014; 128(4):551-9. DOI: 10.1007/s00401-014-1326-7. View