title: Molecular stereotactic biopsy technique improves diagnostic accuracy and enables personalized treatment strategies in glioma patients.
abstract: BACKGROUND
  In gliomas molecular biomarkers are increasingly gaining diagnostic, prognostic and predictive significance. Determination of biomarker status after biopsy is important as not all patients are eligible for open tumor resection. We developed and validated prospectively (6/10-12/11) a protocol allowing for both reliable determination of multiple biomarkers and representative histological diagnoses from small-sized biopsies.
  
  
  METHODS
  All molecular stereotactic biopsies were performed according to a detailed workflow. The selection of specimens best suited for molecular analyses was intra-operatively guided by the attending neuropathologist. Postoperative screening was done by methylation specific PCR using two distinct cryopreserved specimens to test for reproducibility of the findings and to rule out contamination. The DNA of a single best-suited specimen (1 mm(3)) was subjected to detailed molecular analysis (MGMT promoter methylation, IDH1/2 mutational status, LOH 1p and/or 19q).
  
  
  RESULTS
  159 consecutively enrolled untreated gliomas were analyzed (94 glioblastomas, 2 gliosarcomas, 24 anaplastic astrocytomas, 10 oligo-tumors grade II/III, 20 grade II astrocytomas and 9 pilocytic astrocytomas). Transient morbidity was 2 %. Overall, the drop-out rate due to tissue contamination was 0.4 %. Median time from biopsy to histological and molecular genetic analyses was 3 and 5 days, respectively. Distributions of the respective biomarker status for tumor subgroups were consistent with the literature. The final histological diagnosis was changed/modified in 5/159 patients according to molecular findings. Treatment after molecular biopsy was highly personalized.
  
  
  CONCLUSIONS
  Molecular stereotactic biopsy is feasible and safe, can be implemented in daily clinical practice, improves diagnostic precision and enables personalized treatment.
authors.affiliation: Center for Neuropathology and Prion Research, University of Munich Medical Center - Grosshadern, Ludwig-Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Eigenbrod
authors.forename: Raimund
authors.initials: R
authors.lastname: Trabold
authors.forename: David
authors.initials: D
authors.lastname: Brucker
authors.forename: Christian
authors.initials: C
authors.lastname: Erös
authors.forename: Rupert
authors.initials: R
authors.lastname: Egensperger
authors.forename: Christian
authors.initials: C
authors.lastname: La Fougere
authors.forename: Werner
authors.initials: W
authors.lastname: Göbel
authors.forename: Adrian
authors.initials: A
authors.lastname: Rühm
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Tonn
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
authors.forename: Armin
authors.initials: A
authors.lastname: Giese
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Kreth
mesh_terms: D000328:Adult; D000367:Age Factors; D014408:Biomarkers, Tumor; D001706:Biopsy; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D005910:Glioma / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D057285:Precision Medicine; D011379:Prognosis; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D013238:Stereotaxic Techniques; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes