Morphological and molecular features of astroblastoma, including BRAF(V600E) mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults

作者：Lehman Norman L; Hattab Eyas M; Mobley Bret C; Usubalieva Aisulu; Schniederjan Matthew J; McLendon Roger E; Paulus Werner; Rushing Elisabeth J; Georgescu Maria Magdalena; Couce Marta; Dulai Mohanpal S; Cohen Mark L; Pierson Christopher R; Raisanen Jack M; Martin Sarah E; Lehman Trang D; Lipp Eric S; Bonnin Jose M; Al Abbadi Mousa A; Kenworthy Kara; Zhao Kevin; Mohamed Nehad; Zhang Guojuan; Zhao Weiqiang

来源：Neuro-Oncology, 2017, 19(1): 31-42.

DOI：10.1093/neuonc/now118

• astroblastoma
• BRAF(V600E) mutation
• IDH1(R132H) mutant protein expression
• MGMT promoter hypermethylation
• Olig2 protein expression

Background. Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose.
Methods. We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffin-embedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan-Meier methods.
Results. Unlike ependymomas and angiocentric gliomas, ABs demonstrate abundant distinctive astroblastic pseudorosettes and are usually Olig2 immunopositive. They also frequently exhibit rhabdoid cells, multinucleated cells, and eosinophilic granular material. They retain immunoreactivity to alpha thalassemia/mental retardation syndrome X-linked, are immunonegative to isocitrate dehydrogenase-1 R132H mutation, and only occasionally show MGMT promoter hypermethylation differentiating them from many diffuse gliomas. Like pleomorphic xanthoastrocytoma, ganglioglioma, supratentorial pilocytic astrocytoma, and other predominantly cortical-based glial tumors, ABs often harbor the BRAF(V600E) mutation, present in 38% of cases tested (n = 21), further distinguishing those tumors from ependymomas and angiocentric gliomas. Factors correlating with longer patient survival included age less than 30 years, female gender, absent BRAF(V600E), and mitotic index less than 5 mitoses/10 high-power fields; however, only the latter was significant by Cox and Kaplan-Meier analyses (n = 24; P = .024 and .012, respectively). This mitotic cutoff is therefore currently the best criterion to stratify tumors into low-grade ABs and higher-grade anaplastic ABs.
Conclusions. In addition to their own characteristic histological features, ABs share some molecular and histological findings with other, possibly ontologically related, cortical-based gliomas of mostly children and young adults. Importantly, the presence of BRAF(V600E) mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.

• 出版日期2017-1