gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

High Genetic Progression Scores (GPS) are predictive for early recurrence and anticipate histopathological malignisation in a case of multi-recurrent intra-cranial meningioma

Meeting Abstract

  • Dennis Kraemer - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg/Saar
  • Steffi Urbschat - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg/Saar
  • Christina Drieß - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg/Saar
  • Stefan Linsler - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg/Saar
  • Joachim Oertel - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg/Saar
  • Ralf Ketter - Neurochirurgische Klinik, Universitätskliniken des Saarlandes, Homburg/Saar

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocDI.09.11

doi: 10.3205/13dgnc249, urn:nbn:de:0183-13dgnc2492

Published: May 21, 2013

© 2013 Kraemer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: In the course of meningioma progression specific recurrent aneusomies occur whose most likely clonal order was deduced from a large series of 661 karyotyped meningioma cases using oncogenetic trees models. Based on this probabilistic framework, a Genetic Progression Score (GPS) has been introduced that univariately quantifies the genetic evolution status and hence allows a more precise inter- and intra-individual comparability of tumor progression. Here we present a case of a 65-year-old man with multi-recurrent fronto-parietal meningioma showing high GPS before malignant transformation and epigenetic alteration in the course of disease.

Method: After complete primary tumour extirpation, the patient intercurrently underwent three recurrent surgeries until he died from sepsis. Intra-individual cytogenetic findings were revealed by conventional GTG-banding and two-colour FISH. The latter analysis was comprehensively performed on intraoperative touch preparations using locus-specific probes detecting the most relevant autosomal losses. Additionally, we subjected all four autologous samples to methylation-specific PCR in order to analyze the promoter hypermethylation of p16INK4A and TIMP3 that have been evidenced to be associated with meningioma progression.

Results: On conventional cytogenetic examination, the primary lesion was already encountered a typical progression associated karyotype showing complexly aberrant chromosome complement with consistent hypodiploidy and clinically unfavourable loss of the short arm of chromosome 1. The resulting cytogenetic signature of combined losses of chromosomes 1p, 14, 18, 22 corresponded to a GPS of 7,35 (>6.02), indicating a high risk of recurrence. For the second recurrence, monosomies of 1p, 9p, 14, 18, and 22 were detected in interphase cells with high mosaic rates (>80%). In line to these findings, losses of 1p and 22 could be confirmed in representative nuclei population of the third recurrent tumour. Interestingly, in epigenetic analyses, the primary tumour and the first recurrence displayed no methylation for p16 and TIMP3, whereas the second and third recurrent samples showed hypermethylation for TIMP3 alone and for both genes, respectively.

Conclusions: This case report highlights the potential of GPS as an early, histology-independent predictor of recurrence. Before histopathological and epigenetic parameters, high GPS may anticipate a malignisation and indicate intrinsic tendency to recur.