J Neurol Surg B Skull Base 2016; 77 - LFP-07-04
DOI: 10.1055/s-0036-1592589

1p36 Loss Is Associated with Regrowth of WHO Grade I Meningiomas after Gamma Knife Radiosurgery

Vincent J. Bulthuis 1, P. J. J. Damen 2, P. E. J. Hanssens 3, Suan Te Lie 3, R. Fleischeuer 4, E. J. M. Speel 2, Jacobus J. van Overbeeke 1
  • 1Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands
  • 2Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
  • 3Gamma Knife center, St Elisabeth Hospital, Tilburg, The Netherlands
  • 4Department of Pathology, St Elisabeth Hospital, Tilburg, The Netherlands

Objectives: WHO grade I meningiomas may show growth after radiosurgical treatment, which can result in the need for additional treatments, for example surgery. It is therefore essential to be able to predict this aggressive behavior, which so far cannot be established with clinical parameters. There is increasing evidence that certain biomarkers are associated with recurrence and regrowth of meningiomas. The aim of this study was to identify biomarkers to predict regrowth of WHO grade I meningiomas after radiosurgery.

Methods: Forty-four with WHO grade I meningiomas who underwent adjuvant radiosurgical treatment after Simpson 3 resection were included in this study, of which 8 showed regrowth. The median time of follow up was 63 months (range: 24–137 months).

Three µm thick tissue sections of formalin-fixed, paraffin embedded tumors were analyzed for the proliferation marker Ki-67 by immunohistochemistry and for deletion of 1p36 by fluorescence in situ hybridization (FISH). Furthermore, genomic DNA was isolated and, after bisulfite treatment, analyzed for promoter hypermethylation of the genes HOXA 9, NDRG 1–4, SFRP 1, and MGMT. Results were correlated with each other and with clinical and follow-up data.

Results: Comparison of meningiomas with and without regrowth after radiosurgery revealed that tumors with regrowth (1) showed more often deletion of 1p36 (62.5 vs. 8.6%, p = 0.001); (2) a higher Ki67 proliferation index (2.0 vs. 1.4%, p = 0.276); (3) increased methylation of NDRG 1 (40 vs. 13.9%, p = 0.046); (4) increased methylation of NDRG 2 (32 vs. 10% (p = 0.31); (5) increased methylation of MGMT (20 vs. 15% (p = 0.87); (6) increased methylation of HOXA 9 (18 vs. 11% (p = 0.40); and (7) decreased methylation of SFRP 1 (14 vs. 18% (p = 0.67). NDRG 3 and 4 were unmethylated in all samples of either group. The presence of a deletion in chromosome 1p36 was the only parameter that was significantly associated with meningioma regrowth after multivariate analysis.

Conclusion: Our results show that deletion of 1p36 is associated with regrowth after Gamma Knife radiosurgery of WHO grade I meningiomas. Deletion of 1p36 therefore might be a putative biomarker for this purpose, if this finding can be confirmed in an independent larger set of tumors. Early detection of aggressive behavior of WHO grade I meningioma can be of importance in the choice of treatment dose, the duration and frequency of follow-up.