Abstract
WHO grade I meningiomas occasionally show regrowth after radiosurgical treatment, which cannot be predicted by clinical features. There is increasing evidence that certain biomarkers are associated with regrowth of meningiomas. The aim of this retrospective study was to asses if these biomarkers could be of value to predict regrowth of WHO grade I meningiomas after additive radiosurgery. Forty-four patients with WHO grade I meningiomas who underwent additive radiosurgical treatment between 2002 and 2015 after Simpson IV resection were included in this study, of which 8 showed regrowth. Median follow-up time was 64 months (range 24–137 months). 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 analyzed for promoter hypermethylation of the genes NDRG1–4, SFRP1, HOXA9 and MGMT. Comparison of meningiomas with and without regrowth after radiosurgery revealed that loss of 1p36 (p = 0.001) and hypermethylation of NDRG1 (p = 0.046) were correlated with regrowth free survival. Loss of 1p36 was the only parameter that was significantly associated with meningioma regrowth after multivariate analysis (p = 0.01). Assessment of 1p36 loss in tumor tissue prior to radiosurgery might be considered an indicator of prognosis/regrowth. However, this finding has to be validated in an independent larger set of tumors.
Highlights
World Health Organization (WHO) grade I meningiomas occasionally show regrowth after radiosurgical treatment, which cannot be predicted by clinical features
Of the 4 family members, the NDRG2 mRNA and protein expression levels were found to be reduced in higher grade and clinically aggressive meningiomas, which was associated with hypermethylation of the NDRG2 promotor[11]
fluorescence in situ hybridization (FISH) for 1p36/1q25 was performed on 43 meningioma samples and 2 nontumoral brain tissue control samples (Fig. 1A-B)
Summary
WHO grade I meningiomas occasionally show regrowth after radiosurgical treatment, which cannot be predicted by clinical features. Forty-four patients with WHO grade I meningiomas who underwent additive radiosurgical treatment between 2002 and 2015 after Simpson IV resection were included in this study, of which 8 showed regrowth. Despite the fact that most WHO grade I meningiomas can be controlled well, a small group shows regrowth after radiosurgery, which is difficult to predict by histopathology on the tissue biopsy prior to treatment. Some studies show that proliferation marker Ki-67 correlates with significantly shorter recurrence-free survival (RFS) in meningiomas of all grades, if for example tumors have a proliferation index > 3%7 or when > 25 positive cell nuclei per square millimetre[8] are observed. Of the 4 family members, the NDRG2 mRNA and protein expression levels were found to be reduced in higher grade and clinically aggressive meningiomas, which was associated with hypermethylation of the NDRG2 promotor[11]. Promotor hypermethylation of O6–methylguanine-DNA methyltransferase (MGMT) has been found in 0–22% in meningiomas and grade II meningiomas showed twofold higher percentage of MGMT promotor methylation than grade I tumor[19,20,21]
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