Molecular Pathology Markers of Morphologic Glioma Type

Oligodendrogliomas have a better prognosis, grade for grade, compared with MOA and astrocytic gliomas. In addition, Cairncross et al. demonstrated in 1994 that some anaplastic oligodendrogliomas respond to combination chemotherapy and radiation therapy.21 Simultaneously, several investigators observed that approximately 70% of oligodendrogliomas have deletions of the chromosome 19 q arm, 70% have deletions of the chromosome 1p arm, and

60% have deletions of both arms (reviewed in Reference 5). Usually, the entire chromosomal arms are deleted.22 In contrast, about 40%, 20%, and 10% of astrocytomas have deletion of 19q, 1p, and both 1p and 19q, respectively.22 The proportion of MOA with 1p and 19q deletions is intermediate, suggesting that some of these tumors can be grouped with the oligodendrogliomas.22,23 A significant proportion of MOA also have P53 mutations and other genetic anomalies, suggesting that these tumors can be grouped with the astrocytomas.22,23

Two retrospective studies have provided evidence that the oligodendrogliomas with 1p deletions, 19q deletions, or both have a better prognosis and respond better to chemotherapy and radiation therapy.24,25 While these results need to be confirmed by prospective trials, the data strongly suggest that 1p/19q deletions are associated with tumors of oligodendroglial lineage, with oligoden-drogliomas that have a better prognosis, and with oligodendrogliomas that respond to chemotherapy and radiation therapy.

Small cell GBM can be confused with high-grade oligodendrogliomas. EGFR amplification is highly prevalent in small cell GBM, occurring in 22 of 30 tumors in one study.26 Thus, the absence of 1p/19q deletions and the presence of EGFR amplification increase the likelihood that gliomas with large numbers of small, relatively regularly shaped cells are likely to be small cell GBM.

Other alterations are thought to be prevalent in oligodendrogliomas that lack 1p and 19q deletions. CDKN2A/CDKN2B/ARF (P16, P15, P19), PTEN, and chromosome 10 are frequently deleted in high-grade oligodendrogliomas. The expression of CDKN2A and CDKN2B often is inactivated by promoter methylation. While the presence of these alterations is associated with a poorer prognosis,24,27,28 their detection has not become a part of standard clinical neurooncology.

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