title: MGMT Promoter Methylation and BRAF V600E Mutations Are Helpful Markers to Discriminate Pleomorphic Xanthoastrocytoma from Giant Cell Glioblastoma.
abstract: Giant Cell Glioblastoma (gcGBM) and Pleomorphic Xanthoastrocytoma (PXA) are rare astroglial tumors of the central nervous system. Although they share certain histomorphological and immunohistochemical features, they are characterized by different clinical behavior and prognosis. Nevertheless, few cases remain uncertain, as their histomorphological hallmarks and immunophenotypes do correspond to the typical pattern neither of gcGBM nor PXA. Therefore, in addition to the routinely used diagnostic histochemical and immunohistochemical markers like Gömöri, p53 and CD34, we analyzed if genetic variations like MGMT promoter methylation, mutations in the IDH1/2 genes, or BRAF mutations, which are actually used as diagnostic, prognostic and predictive molecular markers in anaplastic glial tumors, could be helpful in the differential diagnostic of both tumor entities. We analyzed 34 gcGBM and 20 PXA for genetic variations in the above-named genes and found distinct distributions between both groups. MGMT promoter hypermethylation was observed in 3 out of 20 PXA compared to 14 out of 34 gcGBM (15% vs. 41.2%, p-value 0.09). BRAF V600E mutations were detected in 50% of the PXA but not in any of the gcGBM (50% vs. 0%, p-value < 0.001). IDH1 R132 and IDH R172 mutations were not present in any of the PXA and gcGBM cases. Our data indicate, that in addition to the histological and immunohistochemical evaluation, investigation of MGMT promoter methylation and in particular BRAF V600E mutations represent reliable additional tools to sustain differentiation of gcGBM from PXA on a molecular basis. Based on these data specific BRAF kinase inhibitors could represent a promising agent in the therapy of PXA and their use should be emphasized.
authors.affiliation: Department of Neuropathology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Laura-Nanna
authors.initials: LN
authors.lastname: Lohkamp
authors.affiliation: Department of Neuropathology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Schinz
authors.affiliation: Department of Neuropathology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Gehlhaar
authors.affiliation: Department of Neuropathology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Guse
authors.affiliation: Department of Neurosurgery and Pediatric Neurosurgery, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Ulrich-Wilhelm
authors.initials: UW
authors.lastname: Thomale
authors.affiliation: Department of Neurosurgery and Pediatric Neurosurgery, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
authors.affiliation: Department of Neuropathology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.affiliation: Department of Neuropathology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Arend
authors.initials: A
authors.lastname: Koch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D057089:Pathology, Molecular; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013702:Temporal Lobe / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D045643:DNA Repair Enzymes