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Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features
Martin J van den Bent1, Leendert H J Looijenga, K Langenberg
1Department of Neurooncology, Erasmus University Medical Center Rotterdam-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. bent@neuh.azr.nl
Background:
Patients who have oligodendrogliomas (OD) that demonstrate loss of both 1p and 19q appear to have a better prognosis after they receive chemotherapy and radiotherapy compared with patients who have OD without these characteristics. It is unclear whether this improvement in outcome is due only to a better response to treatment. The authors investigated the correlation between genetic and clinical characteristics of OD in 33 patients who received chemotherapy with procarbazine, lomustine, and vincristine for recurrent disease after receiving radiotherapy.
Methods:
The initial presentation, prior treatments, overall survival, and response to chemotherapy were assessed. The 1p and 19q status in OD lesions was determined with fluorescence in situ hybridization on paraffin embedded, archival material using locus specific probes. P53 mutations were assessed by polymerase chain reaction-single-strand conformation polymorphism analysis and immunohistochemistry for P53; the proliferation index was assessed with the MIB-1 antibody.
Results:
Patients who had OD lesions with a combined loss of 1p and 19q typically presented with low-grade tumors that manifested with seizures of long-standing duration. In contrast, patients who had OD lesions without a combined loss of 1p and 19q usually presented with focal deficits that required immediate treatment. Both the response rate to chemotherapy and the time to disease progression after chemotherapy were significantly better in patients who had a combined loss of 1p and 19. Tumors with classic OD morphology more often had a combined loss of 1p and 19q, although the genotype was better at identifying patients with chemoresponsive tumors. P53 mutations were observed in three tumors, none of which had a combined loss of 1p and 19q.
Conclusions:
OD lesions with combined a loss of 1p and 19q have a more indolent nature compared with OD lesions that do not have these losses. Virtually all patients with these tumors present with low-grade tumors accompanied by seizures and remain stable for prolonged periods. Future trials must keep these tumor types apart.