Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials

• Published in: Journal of clinical oncology Vol. 33; no. 17; pp. 1943 - 1950
• Main Authors: Kros, Johan M., Huizer, Karin, Hernández-Laín, Aurelio, Marucci, Gianluca, Michotte, Alex, Pollo, Bianca, Rushing, Elisabeth J., Ribalta, Teresa, French, Pim, Jaminé, David, Bekka, Nawal, Lacombe, Denis, van den Bent, Martin J., Gorlia, Thierry
• Format: Journal Article
• Language: English
• Published: United States 10.06.2015
• Subjects: Adult; Aged; Algorithms; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Brain Neoplasms - chemistry; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Chromosome Deletion; Chromosomes, Human, Pair 10 - genetics; Chromosomes, Human, Pair 7 - genetics; DNA Methylation; DNA Modification Methylases - genetics; DNA Repair Enzymes - genetics; Evidence-Based Medicine; Female; Gene Amplification; Glioma - chemistry; Glioma - genetics; Glioma - pathology; Humans; Isocitrate Dehydrogenase - genetics; Male; Microscopy; Middle Aged; Mutation; Proportional Hazards Models; Receptor, Epidermal Growth Factor - genetics; Tumor Suppressor Proteins - genetics; User-Computer Interface
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2014.59.0166

With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. Our project aimed to construct a diagnostic algorithm for gliomas based on molecular and histologic parameters with independent prognostic values. The pathology slides of 636 patients with gliomas who had been included in EORTC 26951 and 26882 trials were reviewed using virtual microscopy by a panel of six neuropathologists who independently scored 18 histologic features and provided an overall diagnosis. The molecular data for IDH1, 1p/19q loss, EGFR amplification, loss of chromosome 10 and chromosome arm 10q, gain of chromosome 7, and hypermethylation of the promoter of MGMT were available for some of the cases. The slides were divided in discovery (n = 426) and validation sets (n = 210). The diagnostic algorithm resulting from analysis of the discovery set was validated in the latter. In 66% of cases, consensus of overall diagnosis was present. A diagnostic algorithm consisting of two molecular markers and one consensus histologic feature was created by conditional inference tree analysis. The order of prognostic significance was: 1p/19q loss, EGFR amplification, and astrocytic morphology, which resulted in the identification of four diagnostic nodes. Validation of the nodes in the validation set confirmed the prognostic value (P < .001). We succeeded in the creation of a timely diagnostic algorithm for anaplastic glioma based on multivariable analysis of consensus histopathology and molecular parameters.