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Clin Cancer Res. 2019 Apr 15;25(8):2656-2663. doi: 10.1158/1078-0432.CCR-18-3101. Epub 2019 Jan 11.

The Misclassification of Diffuse Gliomas: Rates and Outcomes.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. jiorgulescu@bwh.harvard.edu.
2
Harvard Medical School, Boston, Massachusetts.
3
Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts.
4
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
5
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
6
Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Center, Boston, Massachusetts.
7
Center for Neuro-Oncology, Department of Medical Oncology, Dana-Farber Cancer Center, Boston, Massachusetts.
8
Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.
9
Department of Pathology, University of California, San Francisco, San Francisco, California.

Abstract

PURPOSE:

The integrated histopathologic and molecular diagnoses of the 2016 WHO classification of central nervous system tumors have revolutionized patient care by improving diagnostic accuracy and reproducibility; however, the frequency and consequences of misclassification of histologically diagnosed diffuse gliomas are unknown.

EXPERIMENTAL DESIGN:

Patients with newly diagnosed ICD-O-3 (International Classification of Diseases) histologically encoded diffuse gliomas from 2010-2015 were identified from the National Cancer Database, the misclassification rates and overall survival (OS) of which were assessed by WHO grade and 1p/19q status. In addition, misclassification rates by isocitrate dehydrogenase (IDH), ATRX, and p53 statuses were examined in an analogous multi-institutional cohort of registry-encoded diffuse gliomas.

RESULTS:

Of 74,718 patients with diffuse glioma, only 74.4% and 78.8% of molecularly characterized WHO grade II and III oligodendrogliomas were in fact 1p/19q-codeleted. In addition, 28.9% and 36.8% of histologically encoded grade II and III "oligoastrocytomas", and 6.3% and 8.8% of grade II and III astrocytomas had 1p/19q-codeletion, thus molecularly representing oligodendrogliomas if also IDH mutant. OS significantly depended on accurate WHO grading and 1p/19q status.

CONCLUSIONS:

On the basis of 1p/19q, IDH, ATRX, and p53, the misclassification rates of histologically encoded oligodendrogliomas, astrocytomas, and glioblastomas are approximately 21%-35%, 6%-9%, and 9%, respectively; with significant clinical implications. Our findings suggest that when compared with historical histology-only classified data, in national registry, as well as, institutional databases, there is the potential for false-positive results in contemporary trials of molecularly classified diffuse gliomas, which could contribute to a seemingly positive phase II trial (based on historical comparison) failing at the phase III stage. Critically, findings from diffuse glioma clinical trials and historical cohorts using prior histology-only WHO schemes must be cautiously reinterpreted.

PMID:
30635340
PMCID:
PMC6467794
[Available on 2020-04-15]
DOI:
10.1158/1078-0432.CCR-18-3101

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