title: BRAF-mutated pleomorphic xanthoastrocytoma is associated with temporal location, reticulin fiber deposition and CD34 expression.
abstract: BRAF V600E mutation and homozygous deletion of CDKN2A (p16) are frequent molecular alterations in pleomorphic xanthoastrocytomas (PXAs). We investigated 49 PXAs for clinical, histological and immunohistochemical characteristics related to BRAF mutation status. BRAF mutation was detected by immunohistochemical assay and DNA sequencing in 38/49 (78%) tumors. All but one PXA located in the temporal lobe harbored a BRAF V600E mutation (23/24; 96%) compared with 10/19 nontemporal PXAs (53%; P = 0.0009). Histological and immunohistochemical analysis demonstrated increased reticulin deposition (76% vs. 27%; P = 0.003) and a more frequent expression of CD34 in BRAF-mutant PXAs (76% vs. 27%; P = 0.003). We further investigated the utility of combined BRAF V600E (VE1) and p16 analysis by immunohistochemistry to distinguish PXAs from relevant histological mimics like giant-cell glioblastoma. Among PXAs, 38/49 (78%) were VE1-positive, and 30/49 (61%) had a loss of p16 expression. The combined features (VE1 positivity/p16 loss) were observed in 25/49 PXAs (51%) but were not observed in giant-cell glioblastoma (VE1 0/28, p16 loss 14/28). We demonstrate that temporal location, reticulin deposition and CD34 expression are associated with BRAF mutation in PXA. Combined VE1 positivity and p16 loss represents a frequent immunoprofile of PXA and may therefore constitute an additional diagnostic tool for its differential diagnosis.
authors.affiliation: Department of Neuropathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany; German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Koelsche
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.forename: Adelheid
authors.initials: A
authors.lastname: Wöhrer
authors.forename: Astrid
authors.initials: A
authors.lastname: Jeibmann
authors.forename: Jens
authors.initials: J
authors.lastname: Schittenhelm
authors.forename: Patricia
authors.initials: P
authors.lastname: Kohlhof
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.forename: Bernd
authors.initials: B
authors.lastname: Romeike
authors.forename: Hildegard
authors.initials: H
authors.lastname: Dohmen-Scheufler
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: Albert
authors.initials: A
authors.lastname: Becker
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: David
authors.initials: D
authors.lastname: Capper
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism*; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012155:Reticulin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005904:Glial Fibrillary Acidic Protein; D012155:Reticulin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF V600E; CD34; CDKN2A; VE1; brain tumor; immunohistochemistry; p16; pleomorphic xanthoastrocytoma