Novel Molecular Stereotactic Biopsy Procedures Reveal Intratumoral Homogeneity of Loss of Heterozygosity of 1p/19q and TP53 Mutations in World Health Organization Grade II Gliomas

Abstract

We report a molecular stereotactic biopsy technique that combines histopathologic diagnosis with small sample size-adjusted molecular genetic analysis of low-grade gliomas that are ineligible for tumor resection. Loss of heterozygosity (LOH) of 1p/19q and TP53 mutations were analyzed in 1-mm tissue samples from 42 World Health Organization grade II gliomas (30 astrocytomas, 8 oligoastrocytomas, 4 oligodendrogliomas) using polymerase chain reaction-based microsatellite and sequence analysis. Alternating histological and molecular genetic evaluation within 1-mm steps at different sites within each tumor was performed to determine reproducibility of the results and the intratumoral distribution of the biomarkers. Multiple serial biopsies (range, 2-5 per tumor) taken from distinct intratumoral areas revealed concordant molecular genetic findings and homogeneous distribution of both biomarkers throughout 41 tumors. Contamination by nonneoplastic tissue could be recognized by corresponding histological evaluation and resulted in discordant LOH findings in 1 tumor. The frequency of LOH 1p/19q and TP53 mutations was consistent with the literature; these genetic alterations were found to be mutually exclusive. There was no biopsy-related morbidity. We conclude that determination of the LOH 1p/19q and TP53 status using this molecular stereotactic biopsy technique is safe and reliable in cases of unresectable gliomas.

Dynamic 18F-FET PET in Newly Diagnosed Astrocytic Low-Grade Glioma Identifies High-Risk Patients

“…PET-guided stereotactic biopsy procedures or neuronavigated microsurgery with MR imaging and PET image fusion (Brainlab) were used to ensure a spatially precise tissuesampling procedure throughout the tumors under investigation (8). The mean number of tissue samples per patient was 5.…”

“…Several prognostic factors influencing the disease course have been proposed, such as patient age, histologic subtype, and tumor diameter (4). Recently, different molecular-genetic factors have been shown to correlate with outcome, in particular TP53 mutations and isocitrate dehydrogenase gene mutation (IDH1) in astrocytic gliomas (5)(6)(7)(8).…”

Serial 18F-FET PET Imaging of Primarily 18F-FET–Negative Glioma: Does It Make Sense?

“…PET-guided stereotactic biopsy procedures or neuronavigated microsurgery with MR and PET image fusion (Brainlab) were used to ensure a spatially precise tissue-sampling procedure throughout the intracerebral tumors (21). Histologic classification and tumor grading were performed according to the current WHO guidelines (22).…”

Dynamic 18F‐FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses

“…This technique also enables a precise correlative and prognostic analysis of imaging, histologial and molecular data. 23 In tumors exhibiting a hot spot, tumor samples clearly inside and outside of hot spots were used for separate histopathological and molecular-genetic analyses (the respective numbers of tumor samles per patient are given in Table 1). Samples were paraffin-embedded for histological examination or snapfrozen for subsequent molecular-genetic analyses.…”