gms | German Medical Science

Objective: Information about the MGMT (O⁶-methyl-guanine DNA methyltransferase) promoter methylation status and LOH (loss of heterozygosity) on 1p and/or 19q becomes increasingly important for prognostic evaluation and treatment decision in glioma patients. The aim of this prospective study (10/2006–10/2007) was to evaluate whether 1. small samples obtained from stereotactic biopsy are sufficient for the determination of the MGMT and LOH status, and 2. extended biopsy procedures (which are necessary for additional molecular-genetic characterization) are associated with an increased risk.

Methods: Molecular stereotactic biopsy was indicated in case of highly eloquent tumor location and/or significant co-morbidity. Multiplanar trajectory planning with the BrainLab navigation software was based on co-registrated CT, MRI, and ¹⁸F-FET PET data. A serial biopsy was taken along a trajectory representative of the solid tumor including the area with the highest FET uptake. The maximum amount of tissue per specimen was 1 mm³. At least two samples collected from different sites were used for molecular-genetic analysis. Methylation-specific PCR for determination of promoter methylation and microsatellite analysis for LOH1p19q were specifically adopted for small sample sizes. Any adverse sequel potentially attributable to the biopsy procedure was considered as morbidity.

Results: 216 patients were included. Histopathological tumor characterization revealed 41 astrocytomas WHO grade II, 47 astrocytomas WHO grade III, 23 oligodendrogliomas / oligoastrocytomas (grade II/III), and 105 glioblastomas. The MGMT and LOH 1p/19q status could be determined in 99,5%; The overall promoter methylation rate was 50% and LOH on 1p/19q was seen in 28%. An isolated allelic loss on 1p or 19q was found in 3% and 8% of patients, respectively. 12–24 tissue samples per tumor were considered necessary by the neurosurgeon and the intra-operatively attending neuropathologist to achieve a sufficient tumor characterization. Tissue samples taken from distinct sites throughout the tumor always revealed the same MGMT and LOH 1p/19q pattern. The transient morbidity rate was 0,48%. There was no permanent morbidity and no mortality.

Conclusions: Because of its homogeneous distribution within each tumor, information about the MGMT promoter methylation and the LOH pattern on 1p and 19q can be reliably obtained from small sized stereotactic biopsies. Extensive but still minimal invasive biopsy procedures can be done with minimal risk using a multimodal imaging guided approach.