1. ¹International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, F-69372 Lyon Cedex 08, France
2. ²Institute of Neuropathology, University Hospital Zurich, CH-8091 Zurich, Switzerland
3. ³Department of Neuropathology, Victor Segalen University, F-33076 Bordeaux, France
4. ⁴Department of Neuropathology, Neurological and Neurosurgical Hospital, Lyon F-69394, France
5. ⁵Department of Neurosurgery, University Hospital Zurich, CH-8091 Zurich, Switzerland

Correspondence: H Ohgaki, E-mail: ohgaki@iarc.fr

Received 18 December 2003; Revised 15 March 2004; Accepted 29 March 2004; Published online 21 June 2004.

Abstract

The histological diagnosis of low-grade astrocytomas and oligodendrogliomas (WHO grade II) is often challenging, particularly in cases that show both astrocytic and oligodendroglial differentiation. We carried out gene expression profiling on 17 oligodendrogliomas (93% with LOH 1p and/or 19q) and 15 low-grade astrocytomas (71% with a TP53 mutation), using a cDNA array containing 1176 cancer-related genes. In oligodendrogliomas, 40 genes showed on average higher expression (at least a two-fold increase) than in astrocytomas, including DES, TDGF1, TGF-, GABA-BR1A, Histone H4, CDKN1A, PCDH43, Rho7 and Jun-D, while 39 genes were expressed at lower levels (at least a two-fold decrease), including JNK2, ITGB4, JNK3A2, RhoC, IFI-56K, AAD14 and EGFR. Immunohistochemistry revealed nuclear staining of Jun-D in oligodendrogliomas, in contrast to the immunoreactivity of cytoplasm and cell processes in low-grade astrocytomas. Partial least-squares analysis of the 79 genes at least two-fold differentially expressed between oligodendrogliomas and low-grade astrocytomas demonstrated perfect separation of oligodendrogliomas from low-grade astrocytomas and normal cerebral white matter. Clustering analysis based on the entire gene set divided the 17 subjects with oligodendrogliomas into two subgroups with significantly different survival (log-rank test, P=0.0305; survival to 5-years, 80 vs 0%, P=0.048). These results demonstrate that oligodendrogliomas and low-grade astrocytomas differ in their gene expression profiles, and that there are subgroups of oligodendroglioma with distinct expression profiles related to clinical outcome.