Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 BRAFV600E 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 BRAFV600E, 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 BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.

Original languageEnglish (US)
Pages (from-to)31-42
Number of pages12
JournalNeuro-Oncology
Volume19
Issue number1
DOIs
StatePublished - 2017

Fingerprint

Neuroepithelial Neoplasms
Glioma
Young Adult
Mutation
Ependymoma
Neuroglia
Astrocytoma
Neoplasms
Ganglioglioma
Isocitrate Dehydrogenase
Mitotic Index
Kaplan-Meier Estimate
Survival Analysis
Mitosis
Paraffin
Formaldehyde
Survival

Keywords

  • Astroblastoma
  • BRAF mutation
  • IDH1 mutant protein expression
  • MGMT promoter hypermethylation
  • Olig2 protein expression

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults. / 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.

In: Neuro-Oncology, Vol. 19, No. 1, 2017, p. 31-42.

Research output: Contribution to journalArticle

Lehman, NL, Hattab, EM, Mobley, BC, Usubalieva, A, Schniederjan, MJ, McLendon, RE, Paulus, W, Rushing, EJ, Georgescu, MM, Couce, M, Dulai, MS, Cohen, ML, Pierson, CR, Raisanen, JM, Martin, SE, Lehman, TD, Lipp, ES, Bonnin, JM, Al-Abbadi, MA, Kenworthy, K, Zhao, K, Mohamed, N, Zhang, G & Zhao, W 2017, 'Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults', Neuro-Oncology, vol. 19, no. 1, pp. 31-42. https://doi.org/10.1093/neuonc/now118
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. / Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults. In: Neuro-Oncology. 2017 ; Vol. 19, No. 1. pp. 31-42.
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abstract = "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 BRAFV600E 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 BRAFV600E, 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 BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.",
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author = "Lehman, {Norman L.} and Hattab, {Eyas M.} and Mobley, {Bret C.} and Aisulu Usubalieva and Schniederjan, {Matthew J.} and McLendon, {Roger E.} and Werner Paulus and Rushing, {Elisabeth J.} and Georgescu, {Maria Magdalena} and Marta Couce and Dulai, {Mohanpal S.} and Cohen, {Mark L.} and Pierson, {Christopher R.} and Raisanen, {Jack M.} and Martin, {Sarah E.} and Lehman, {Trang D.} and Lipp, {Eric S.} and Bonnin, {Jose M.} and Al-Abbadi, {Mousa A.} and Kara Kenworthy and Kevin Zhao and Nehad Mohamed and Guojuan Zhang and Weiqiang Zhao",
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TY - JOUR

T1 - Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults

AU - Lehman, Norman L.

AU - Hattab, Eyas M.

AU - Mobley, Bret C.

AU - Usubalieva, Aisulu

AU - Schniederjan, Matthew J.

AU - McLendon, Roger E.

AU - Paulus, Werner

AU - Rushing, Elisabeth J.

AU - Georgescu, Maria Magdalena

AU - Couce, Marta

AU - Dulai, Mohanpal S.

AU - Cohen, Mark L.

AU - Pierson, Christopher R.

AU - Raisanen, Jack M.

AU - Martin, Sarah E.

AU - Lehman, Trang D.

AU - Lipp, Eric S.

AU - Bonnin, Jose M.

AU - Al-Abbadi, Mousa A.

AU - Kenworthy, Kara

AU - Zhao, Kevin

AU - Mohamed, Nehad

AU - Zhang, Guojuan

AU - Zhao, Weiqiang

PY - 2017

Y1 - 2017

N2 - 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 BRAFV600E 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 BRAFV600E, 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 BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.

AB - 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 BRAFV600E 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 BRAFV600E, 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 BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.

KW - Astroblastoma

KW - BRAF mutation

KW - IDH1 mutant protein expression

KW - MGMT promoter hypermethylation

KW - Olig2 protein expression

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U2 - 10.1093/neuonc/now118

DO - 10.1093/neuonc/now118

M3 - Article

C2 - 27416954

AN - SCOPUS:85014047558

VL - 19

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