Adult pilocytic astrocytomas: clinical features and molecular analysis
Brett J Theeler1, Benjamin Ellezam1, Zsila S Sadighi1
1Department 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.).
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.
Conclusion:
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.
