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Molecular classification of low-grade diffuse gliomas.

Young-Ho Kim1, Sumihito Nobusawa, Michel Mittelbronn

  • 1International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France.

The American Journal of Pathology
|November 16, 2010
PubMed
Summary

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Genetic profiling of diffuse gliomas reveals TP53 mutations predict shorter survival, while 1p/19q loss indicates longer survival. This molecular classification offers an objective alternative to subjective histological diagnoses for grade II gliomas.

Area of Science:

  • Neuro-oncology
  • Molecular Pathology
  • Cancer Genetics

Background:

  • Current World Health Organization classification of grade II diffuse gliomas includes astrocytoma, oligoastrocytoma, and oligodendroglioma.
  • Diagnostic criteria for these histological types, especially oligoastrocytoma, are subjective and lack precision.
  • There is a need for objective methods to classify diffuse gliomas and predict patient outcomes.

Purpose of the Study:

  • To establish genetic profiles for diffuse gliomas.
  • To evaluate the predictive impact of genetic mutations and chromosomal loss on clinical outcomes.
  • To determine if molecular classification can overcome diagnostic ambiguities in low-grade gliomas.

Main Methods:

  • Screening of 360 World Health Organization grade II gliomas for IDH1, IDH2, and TP53 gene mutations.

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  • Assessment for 1p/19q chromosomal loss.
  • Correlation of genetic findings with clinical outcomes, including survival.
  • Multivariate analysis adjusting for age and treatment.

    • Main Results:

    • 86% of tumors were genetically characterized by combinations of IDH1/2 mutation, TP53 mutation, or 1p/19q loss.
    • TP53 mutation ± IDH1/2 mutation was associated with significantly shorter median survival (51.8 months) compared to 1p/19q loss ± IDH1/2 mutation (58.7 months).
    • Multivariate analysis confirmed TP53 mutation as a negative prognostic marker and 1p/19q loss as a positive prognostic marker, while IDH1/2 mutations were not prognostic.

    Conclusions:

    • Molecular classification based on IDH1/2 mutation, TP53 mutation, and 1p/19q loss provides objective diagnostic power comparable to histological classification.
    • This genetic approach circumvents the diagnostic subjectivity associated with oligoastrocytoma.
    • Genetic profiling offers a robust method for predicting survival in patients with grade II diffuse gliomas.