Prognostic and radiographic correlates of a prospectively collected molecularly profiled cohort of IDH1/2-wildtype astrocytomas Journal Article


Authors: Lin, A. L.; Rosenblum, M.; Mellinghoff, I. K.; Tabar, V. S.; Ogilvie, S.; Schaff, L.; Yang, T. I. J.; Young, R. J.; Taylor, B. S.; Jonsson, P.; Bale, T. A.
Article Title: Prognostic and radiographic correlates of a prospectively collected molecularly profiled cohort of IDH1/2-wildtype astrocytomas
Abstract: Background: In the molecular era, the relevance of tumor grade for prognostication of IDH1/2-wildtype (WT) gliomas has been debated. It has been suggested that histologic grade II and III astrocytomas with molecular features of glioblastoma, IDH1/2-WT have a similar prognosis to glioblastoma and should be considered for the same clinical trials. Methods: We integrated prospective clinical sequencing from 564 patients with IDH1/2-WT gliomas (26 grade II, 71 grade III and 467 grade IV) with clinical and radiographic data to assess associations between molecular features, grade and outcome. Results: Compared to histologic grade IV IDH1/2-WT astrocytomas, histologic grade II astrocytomas harbor fewer chromosome 7/10 alterations (P = 0.04), EGFR amplifications (P = 0.022) and alterations in cell-cycle effectors (P = 1.9e-11), but a similar frequency of TERT promoter mutations. In contrast, there is no difference in the frequency of these canonical molecular features in histologic grade III vs. IV IDH1/2-WT disease. Progression-free (PFS) and overall survival (OS) for histologic grade II tumors were significantly longer than grade III tumors (P = 0.02 and P = 0.008, respectively), whereas there was no difference in PFS and OS for histologic grade III compared to grade IV tumors. Median PFS for histologic grade II, III and IV tumors was 19, 11 and 9 months, respectively. Median OS for the same tumors was 44, 23 and 23 months, respectively. In histologic grade II and III IDH1/2 WT tumors, gliomatosis is associated with the absence of cell-cycle alterations (P = 0.008) and enriched in grade II features (P = 0.1) and alterations in the PI3K-AKT pathway (P = 0.09). Conclusions: Grade II histology has genotypic and phenotypic associations with prognostic implications in IDH1/2-WT astrocytomas. © 2020 International Society of Neuropathology
Keywords: adult; controlled study; human tissue; aged; gene mutation; major clinical study; overall survival; promoter region; sequence analysis; single nucleotide polymorphism; clinical feature; outcome assessment; glioma; cancer grading; prospective study; progression free survival; epidermal growth factor receptor; gliosis; cohort analysis; histology; chromosome aberration; glioblastoma; telomerase reverse transcriptase; genomics; methylated dna protein cysteine methyltransferase; gene dosage; astrocytoma; b raf kinase; neuropathology; histologic grade; chromosome 7; isocitrate dehydrogenase 1; chromosome 10; genotype phenotype correlation; clinical outcome; pi3k/akt signaling; cancer prognosis; brain radiography; isocitrate dehydrogenase 2; prognosis; human; male; female; article; idh1/2-wildtype
Journal Title: Brain Pathology
Volume: 30
Issue: 3
ISSN: 1015-6305
Publisher: Blackwell Publishing  
Date Published: 2020-05-01
Start Page: 653
End Page: 660
Language: English
DOI: 10.1111/bpa.12826
PUBMED: 31984581
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Robert J Young
    139 Young
  2. Viviane S Tabar
    141 Tabar
  3. Marc Rosenblum
    331 Rosenblum
  4. T. Jonathan Yang
    81 Yang
  5. Barry Stephen Taylor
    194 Taylor
  6. Shahiba Q Ogilvie
    19 Ogilvie
  7. Karl Philip Jonsson
    43 Jonsson
  8. Andrew Lee Lin
    25 Lin
  9. Lauren Rhea Schaff
    11 Schaff
  10. Tejus Bale
    17 Bale