Alterations of Chromosome Arms 1p and 19q as Predictors of Survival in Oligodendrogliomas, Astrocytomas, and Mixed Oligoastrocytomas

TLDR

Alterations of chromosome arms 1p and 19q have been linked to chemotherapeutic response and overall survival in anaplastic oligodendroglioma, but this association has not been observed in astrocytic tumors, suggesting a potential benefit of integrating histologic and genotypic assessment for patient stratification. The study aimed to clarify the diagnostic and prognostic implications of 1p/19q alterations across a broader spectrum of diffuse gliomas, including astrocytomas and low‑grade oligodendrogliomas. Researchers performed fluorescence in situ hybridization on 162 diffuse gliomas (79 astrocytomas, 52 oligodendrogliomas, and 31 mixed oligoastrocytomas) to enumerate 1p and 19q deletion signals as part of a prospective CNS tumor investigation. Combined loss of chromosome arms 1p and 19q is strongly associated with the oligodendroglial phenotype and independently predicts prolonged overall survival in pure oligodendroglioma patients, whereas this association is absent in astrocytoma and mixed oligoastrocytoma cases.

Abstract

PURPOSE: A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine, lomustine, and vincristine chemotherapy. We set out to further clarify the diagnostic and prognostic implications of these alterations in a broader set of diffuse gliomas, including astrocytic neoplasms and low-grade oligodendrogliomas. PATIENTS AND METHODS: Fluorescence in situ hybridization (FISH) signals from DNA probes mapping to 1p and 19q common deletion regions were enumerated in 162 diffuse gliomas (79 astrocytomas, 52 oligodendrogliomas, and 31 mixed oligoastrocytomas), collected as part of an ongoing prospective investigation of CNS tumors. RESULTS: The oligodendroglial phenotype was highly associated with loss of 1p (P = .0002), loss of 19q (P < .0001), and combined loss of 1p and 19q (P < .0001). Combined loss of 1p and 19q was identified as a univariate predictor of prolonged overall survival among patients with pure oligodendroglioma (log-rank, P = .03) and remained a significant predictor after adjusting for the effects of patient age and tumor grade (P < .01). This favorable association was not evident in patients with astrocytoma or mixed oligoastrocytoma. CONCLUSION: Combined loss of 1p and 19q is a statistically significant predictor of prolonged survival in patients with pure oligodendroglioma, independent of tumor grade. Given the lack of this association in patients with astrocytic neoplasms and the previously demonstrated chemosensitivity of oligodendrogliomas, a combined approach of histologic and genotypic assessment could potentially improve existing strategies for patient stratification and management.