Adult pilocytic astrocytomas: clinical features and molecular analysis.
BACKGROUND
Adult pilocytic astrocytomas (PAs) are rare and have an aggressive clinical course compared with pediatric patients. Constitutive Ras/RAF/MAPK signaling appears to be an important oncogenic event in sporadic PA. We evaluated clinical data and molecular profiles of adult PAs at our institution.


METHODS
We identified 127 adult PAs in our institutional database. Cases with available tissue were tested for BRAF-KIAA1549 fusion/duplication (B-K fusion) by fluorescence in situ hybridization and submitted for mutation profiling using the Sequenom mutation profiling panel. Subgroup analyses were performed based on clinical and molecular data.


RESULTS
The majority of adult PAs are supratentorial. Twenty-two percent of cases had an initial pathologic diagnosis discordant with the diagnosis made at our institution. Recurrence was seen in 42% of cases, and 13% of patients died during follow-up. Adjuvant radiotherapy following surgical resection was associated with a statistically significant decrease in progression-free survival (P = .004). B-K fusion was identified in 20% (9 of 45) of patients but was not associated with outcome. No BRAF V600E mutations (0 of 40 tested) were found.


CONCLUSIONS
This was the largest single institution series of adult PA. A significant proportion of adult PAs follow an aggressive clinical course. Our results support a period of observation following biopsy or surgical resection. B-K fusion in adult PA does not influence outcome, and BRAF V600E mutation appears to be a very rare event. Further study of tumor biology and optimal treatment is needed, given a more aggressive clinical behavior.
Department of Neurology and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland (B.J.T.); Department of Pathology; CHU Sainte-Justine, Universite de Montreal, Montréal Quebec, Canada (B.E.); Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (Z.S.S.); Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas (V.M., M.D.T., A.M.A.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.M.B.); Department of Neurosurgery, The Ohio State University Arthur G. James Cancer Hospital, Columbus, Ohio (V.K.P.).
Brett J
BJ
Theeler
Department of Neurology and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland (B.J.T.); Department of Pathology; CHU Sainte-Justine, Universite de Montreal, Montréal Quebec, Canada (B.E.); Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (Z.S.S.); Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas (V.M., M.D.T., A.M.A.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.M.B.); Department of Neurosurgery, The Ohio State University Arthur G. James Cancer Hospital, Columbus, Ohio (V.K.P.).
Benjamin
B
Ellezam
Department of Neurology and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland (B.J.T.); Department of Pathology; CHU Sainte-Justine, Universite de Montreal, Montréal Quebec, Canada (B.E.); Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (Z.S.S.); Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas (V.M., M.D.T., A.M.A.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.M.B.); Department of Neurosurgery, The Ohio State University Arthur G. James Cancer Hospital, Columbus, Ohio (V.K.P.).
Zsila S
ZS
Sadighi
Department of Neurology and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland (B.J.T.); Department of Pathology; CHU Sainte-Justine, Universite de Montreal, Montréal Quebec, Canada (B.E.); Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (Z.S.S.); Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas (V.M., M.D.T., A.M.A.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.M.B.); Department of Neurosurgery, The Ohio State University Arthur G. James Cancer Hospital, Columbus, Ohio (V.K.P.).
Vidya
V
Mehta
Department of Neurology and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland (B.J.T.); Department of Pathology; CHU Sainte-Justine, Universite de Montreal, Montréal Quebec, Canada (B.E.); Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (Z.S.S.); Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas (V.M., M.D.T., A.M.A.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.M.B.); Department of Neurosurgery, The Ohio State University Arthur G. James Cancer Hospital, Columbus, Ohio (V.K.P.).
M Diep
MD
Tran
Department of Neurology and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland (B.J.T.); Department of Pathology; CHU Sainte-Justine, Universite de Montreal, Montréal Quebec, Canada (B.E.); Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (Z.S.S.); Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas (V.M., M.D.T., A.M.A.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.M.B.); Department of Neurosurgery, The Ohio State University Arthur G. James Cancer Hospital, Columbus, Ohio (V.K.P.).
Adekunle M
AM
Adesina
Department of Neurology and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland (B.J.T.); Department of Pathology; CHU Sainte-Justine, Universite de Montreal, Montréal Quebec, Canada (B.E.); Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (Z.S.S.); Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas (V.M., M.D.T., A.M.A.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.M.B.); Department of Neurosurgery, The Ohio State University Arthur G. James Cancer Hospital, Columbus, Ohio (V.K.P.).
Janet M
JM
Bruner
Department of Neurology and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland (B.J.T.); Department of Pathology; CHU Sainte-Justine, Universite de Montreal, Montréal Quebec, Canada (B.E.); Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (Z.S.S.); Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas (V.M., M.D.T., A.M.A.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.M.B.); Department of Neurosurgery, The Ohio State University Arthur G. James Cancer Hospital, Columbus, Ohio (V.K.P.).
Vinay K
VK
Puduvalli
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000175:diagnosis* / Q000235:genetics; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
C568616:BRAF-KIAA1549 fusion protein, human; D015514:Oncogene Proteins, Fusion
BRAF mutation; low-grade astrocytoma; pilocytic astrocytoma