[1801] Immunohistochemistry of Pediatric CNS Tumors: Mutated IDH1 and the Hippo Pathway

Maria Martinez-Lage, Lisa M Sullivan, Mariarita Santi. Hospital of the University of Pennsylvania, Philadelphia, PA; The Children's Hospital of Philadephia, Philadelphia, PA

Background: Mutations of IDH1 are implicated in adult gliomas, rarely in children. Conversely, the hippo signaling pathway may be involved in brain tumors common in children. We report the frequency of R132H IDH1 mutations and evaluate components of the hippo pathway (CD44, NF2/merlin and YAP-1) in a series of pediatric CNS tumors.
Design: We analyzed 143 pediatric CNS tumors using tissue microarrays: 26 medulloblastomas/PNET, 21 pilocytic astrocytomas, 14 astrocytomas, 13 gangliogliomas, 12 glioblastomas, 12 ependymomas, 11 choroid plexus tumors, 10 meningiomas, 8 DNET, 8 oligodendrogliomas, 4 craniopharyngiomas, 2 germinomas, and 2 central neurocytomas. We interpreted positive staining as follows: cytoplasmic for mutated IDH1, membranous and/or cytoplasmic for CD44 and NF2/merlin (weak vs strong), and nuclear for YAP-1 (1-10% low vs >10% high).
Results: Mutated IDH1 expression was seen in 1/28 diffuse gliomas (3.6%, an oligodendroglioma with 1p19q co-deletion), and in 1/13 gangliogliomas (7.7%). CD44 was widely expressed in glial and glioneuronal neoplasms, germinomas, craniopharyngiomas and meningiomas (75-100%), whereas expression was less frequent in medullobastoma/PNET (55.5%) and neurocytomas (50%). Strong expression was seen in gangliogliomas and pilocytic astrocytomas. NF2/merlin was frequently seen in gliomas, DNET (strong), ependymomas, neurocytomas, choroid plexus tumors, meningiomas, medulloblastoma/PNET and gangliogliomas (77-100%), but was less often seen in germinomas (37%). YAP-1 showed frequent high expression in choroid plexus tumors, ependymomas and meningiomas, and frequent low expression in DNET, pilocytic astrocytomas, diffuse astrocytomas and glioblastomas (75-100%). Oligodendrogliomas, neurocytomas, craniopharyngiomas, gangliogliomas and germinomas expressed YAP-1 in 50-67%, while 37% of medulloblastomas expressed YAP1 with a tendency to show high expression and no association by subtype.
Conclusions: 1) R132H IDH1 mutations are rare in childhood gliomas, and positive cases may behave as adult neoplasms, while the majority follows IDH-independent pathways. 2) YAP-1 and hippo related proteins CD44 and NF2/merlin play a role in a wide range of pediatric brain tumors. 3) High YAP1 expression in ependymomas and meningiomas, with weak NF2/merlin expression is relevant given the predisposition of patients with NF2 to develop these tumors, and possibly reflects downstream upregulation of YAP1 secondary to NF2/merlin deficiencies.
Category: Neuropathology

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 260, Tuesday Afternoon


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