MTOR activation is increased in pilocytic astrocytomas from older adults compared with children

Abstract

Background: Recent studies suggest that the behavior and biology of WHO grade I pilocytic astrocytomas (PAs) in adults is different than that associated with grade I PAs in children. Methods: We evaluated Ki-67 labeling, BRAF abnormalities, isocitrate dehydrogenase R132 immunoreactivity phosphorylation (activation) of p44/42 mitogen activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) in formalin-fixed tissue from 21 adult (18 years or older, mean age 37 years) and 10 children (mean age 9.4 years) WHO grade I PAs. Results: The mean Ki-67 labeling was 4.8% in adults and 3.8% in children. There was no significant difference between Ki-67 labeling in children and adults or either subgroups of adults. No differences were found in phospho p44/42MAPK in adult subgroups (18-33 years and 34 and older) compared to children. Activation/phosphorylation of mTOR was biphasic in adults being significantly lower than children in young adults but significantly higher than children in older adults (age 34 and older). Conclusions: Identifying mTOR phosphorylation/activation may represent a difference in biology and a new marker to guide chemotherapy with recently approved mTOR inhibitors.