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The epidermal growth factor receptor (EGFR) gene is frequently amplified and mutated in high-grade glioma (HGG). Immunohistochemical staining for the EGFRvIII mutant is a negative prognostic factor for patients with anaplastic glioma (Buckner et al., J. Clin. Oncol. 22 (14S), 1508, 2004). We investigated the prognostic and predictive value of EGFR-gene amplification determined with fl uorescence in situ hybridization (FISH) in HGG treated with temozolomide (Temodal, TMZ) at recurrence following surgery and radiotherapy. Clinical data and tumor material were collected from a retrospective cohort of patients treated at 4 Belgian hospitals. All patients were treated with TMZ at recurrence. In addition to conventional diagnostic histopathology, HGG were characterized by FISH for the amplification status of the EGFR-gene (Vysis, LSI EGFR/CEP 7 Dual Color Probe). Our patient population consisted of 36 men and 22 women (N 58) with a median age of 58 years (range, 16-80 years). At the initiation of TMZ treatment, tumors consisted of 14 AA/AOA and 44 GBM. Eighteen tumors were found to have an amplification of the EGFR gene (4/14 AA/AOA, 14/44 GBM). No signifi cant association was found between EGFR-gene amplifi cation and sex, age (at diagnosis or at initiation of TMZ), glioma localization, type of surgery (resection versus biopsy), histology (at diagnosis or at initiation of TMZ), the interval between diagnosis of HGG and the initiation of TMZ, or response to TMZ (objective response or disease control). We found no signifi cant correlation between EGFR-gene amplification and time to progression or overall survival following the initiation of TMZ treatment (Kaplan-Meier survival statistics, log-rank test, P

Between June 1995 and November 1998, 228 patients with relapsing-remitting Multiple Sclerosis started treatment with glatiramer acetate (Copaxone) 20 mg once daily in the frame of a "compassionate use" protocol in 15 Belgian centers. Following an average treatment period of 5.8 years, treating neurologists were requested to fill in follow-up forms indicating neurological disability status and side effects during the previous 6 months. These data were available for 134 patients. In this group, the Expanded Disability Status Scale (EDSS) improved in 26.3% of patients. An additional 36.8% of patients remained neurologically stable. The Ambulation Index (AI) showed similar results: 12.5% of patients improved, 50% of patients remained stable, and 37.5% worsened. Only 10% of patients dropped out due to several reasons. The adverse events occurring in the period preceding the follow-up survey were non-serious and consistent with the current product information of glatiramer acetate. Among the 94 patients no longer followed-up in the compassionate program, reasons for lost to follow-up were obtained for 63; most of them (41) had stopped GA treatment or switched to another disease-modifying treatment. Overall these results are very similar to the ones reported in the extension study of the pivotal trial (Johnson et al., 2000), and indicate that patients treated with glatiramer acetate have a better outcome than expected on the basis of the natural course of the disease. Despite limitations of the study design, this report confirms the sustained efficacy of glatiramer acetate in reducing the disease progression in patients with relapsing-remitting multiple sclerosis treated in day-to-day clinical practice.

Background: Tumor specific molecular-genetic features determine the prognosis and sensitivity to alkylating agents of central nervous system gliomas. The O6-methylguanine-DNA-methyltransferase (MGMT) gene promoter is often hypermethylated in high-grade gliomas (HGG) and is a major determinant of the sensitivity to alkylating agents. The tumor suppressor gene p53 is a frequent target for mutation but its importance as a prognostic or predictive marker has not been established. We investigated the correlation between MGMT methylation status and p53 immunohistochemical staining and the benefit from treatment with temozolomide in patients with recurrent HGG. Patients and Methods: A real-time, quantitative methylation-specific PCR (QMSP) assay for the determination of the MGMT promoter methylation status and immunohistochemical staining for p53 TSG were performed on archival tissue blocks from 38 glioma patients (22 with glioblastoma, 12 with anaplastic astrocytoma [AA], and 4 with anaplastic oligoastrocytoma [AOA], treated with temozolomide at first recurrence. In addition we performed fluorescence in situ hybridization for the characterization of chromosomal loss of 1p, 19q and the 17p13.1 locus (p53) and for gains of the EGFR locus. Results: WHO differentiation grade, MGMT methylation status were significantly correlated with time to progression following temozolomide at first recurrence (Cox logistic regression analysis). Within the subgroups of grade III and IV glioma, significance for these two baseline variables was only observed for patients with anaplastic (oligo)astrocytoma. In this subgroup, as opposed to glioblastoma patients, TP53 IHC positivity more strongly predicted a favourable TTP. None of these 16 anaplastic gliomas had loss of 1p or 19q or amplification of EGFR. MGMT promoter methylation correlated with superior overall survival following temozolomide in patients with AA/AOA but not glioblastoma. Conclusions: The synchronous presence of both MGMT promoter methylation and p53 IHC status appear to be useful molecular markers to predict favourable survival following temozolomide at recurrence only in patients with anaplastic oligoastrocytoma without 1p/19q loss or EGFR amplification.