BRAF‐Mutated Pleomorphic Xanthoastrocytoma is Associated with Temporal Location, Reticulin Fiber Deposition and CD34 Expression. (29th January 2014)

• Record Type: Journal Article
• Authors: Koelsche, Christian; Sahm, Felix; Wöhrer, Adelheid; Jeibmann, Astrid; Schittenhelm, Jens; Kohlhof, Patricia; Preusser, Matthias; Romeike, Bernd; Dohmen‐Scheufler, Hildegard; Hartmann, Christian; Mittelbronn, Michel; Becker, Albert; von, Andreas; Capper, David
• Is Part Of: Brain pathology. Volume 24:Number 3(2014:May)
• Page Start: 221
• Page End: 229
• Publication Date: 2014-01-29
• Subjects: Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/bpa.12111
• Languages: English
• ISSNs: 1015-6305

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p> <italic>BRAF</italic> V600E mutation and homozygous deletion of <italic>CDKN2A</italic> (p16) are frequent molecular alterations in pleomorphic xanthoastrocytomas (PXAs). We investigated 49 PXAs for clinical, histological and immunohistochemical characteristics related to <italic>BRAF</italic> mutation status. <italic>BRAF</italic> 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 <italic>BRAF</italic> V600E mutation (23/24; 96%) compared with 10/19 nontemporal PXAs (53%; <italic>P</italic> = 0.0009). Histological and immunohistochemical analysis demonstrated increased reticulin deposition (76% vs. 27%; <italic>P</italic> = 0.003) and a more frequent expression of CD34 in <italic>BRAF</italic>‐mutant PXAs (76% vs. 27%; <italic>P</italic> = 0.003).</p> <p>We further investigated the utility of combined <italic>BRAF</italic> 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 <italic>BRAF</italic> 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.</p> </abstract>