Molecular prognostic factors of anaplastic oligodendroglial tumors and its relationship: a single institutional review of 77 patients from China

Nov 1, 2011Neuro-oncology

Molecular markers linked to outcomes in aggressive brain tumors: a review of 77 patients from China

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Abstract

Seventy-seven patients with oligodendroglial tumors were analyzed to identify prognostic factors associated with overall survival.

Loss of heterozygosity (LOH) on chromosomes 1p and 19q may be linked to increased chemosensitivity in oligodendroglial tumors.
Age at diagnosis, LOH 1p and 19q, IDH1 mutation, and reoperation after progression are identified as independent predictors for longer survival.
MGMT promoter methylation is nonrandomly associated with LOH 1p and LOH 19q.
Mutual exclusion is observed between MGMT promoter methylation and MGMT expression level.
The study highlights the importance of molecular alterations in future clinical trials for anaplastic oligodendroglioma and oligoastrocytoma.

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The increased chemosensitivity of oligodendroglial tumors has been associated with loss of heterozygosity (LOH) on chromosomes 1p and 19q. Other clinical and molecular factors have also been identified as being prognostic and predictive for treatment outcome. Seventy-seven patients with anaplastic oligodendroglioma (AO) or anaplastic oligoastrocytoma (AOA), treated in Beijing Tiantan Hospital from 2006 through 2008, were reviewed. LOH 1p, LOH 19q, IDH1 mutation, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and protein expression level of MGMT, P53, EGFR, and Ki-67 were evaluated. Age at diagnosis, LOH 1p and 19q, IDH1 mutation, P53 expression level, reoperation when progression, and adjuvant chemotherapy were statistically significant factors for overall survival (OS) in univariate analysis. Further multivariate analysis showed that age at diagnosis (P = .010), LOH 1p and 19q (P = .016), IDH1 mutation (P = .011), and reoperation after progression (P = .048) were independent predictors for longer survival in these patients. Nonrandom associations were found between LOH 1p and LOH 19q, MGMT promoter methylation and LOH 1p or 19q, IDH1 mutation and LOH 1p and 19q, IDH1 mutation and MGMT promoter methylation, whereas mutual exclusion was found between MGMT promoter methylation and MGMT expression level. The present study confirmed that age at diagnosis, LOH 1p and 19q, IDH1 mutation, and reoperation after progression were independent significant prognostic factors for patients with anaplastic oligodendroglial tumors. Inter-relationship between LOH 1p, LOH 19q, IDH1 mutation, MGMT promoter methylation, and MGMT expression level were also revealed. Future clinical trials for AO and AOA should consider the molecular alterations of patients.

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Molecular prognostic factors of anaplastic oligodendroglial tumors and its relationship: a single institutional review of 77 patients from China

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